Children learn words using a range of social, statistical, and perceptual information. One proposal for how childrendetermine word meanings is cross-situational learning, in which children track ambiguous word-object mappings overtime (e.g., Yu & Smith, 2007). However, previous studies have not evaluated how children use natural social cues duringlearning (e.g., eye gaze). We taught 3-year-olds three novel verbs (c.f., Scott & Fisher, 2012) and hypothesized that socialcues not only support cross-situational learning, but also support retention of verbs after a delay. In between-subjectsconditions, children either did or did not have access to eye-gaze and head-turn cues during exposure. We tested forparticipants learning after 12 learning trials and after a delay. Pilot data suggest that children who have access to naturalsocial cues successfully learned and retained links between novel verbs and their corresponding actions.

Accessibility plays a major role in speech production. Here we investigate and measure four factors that influence speakers to produce one word over another more optimal word form. Three experiments asked participants to label images of insects and instruments. Participants were incentivized to produce an accurate specific label (e.g., bee), over a more general label (e.g., insect), so that specific labels were more optimal. Each of three experiments manipulated a different factor that could influence accessibility – word frequency, priming, and interference – and all experiments additionally varied whether labels had to be produced under time pressure or not. Results showed that each variable significantly influenced the accessibility of labels: participants produced more specific labels when those labels were higher frequency, when they were primed, when a visually-similar label had not been primed, and when participants were unconstrained by time pressure. These findings demonstrate that multiple factors influence the accessibility of familiar words during production, regularly leading participants to rely on “good-enough” rather than optimal options to convey their message.

The unfolded protein response (UPR) adjusts the cell's protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α's ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD's MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1's activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.

Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m² ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m² ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.