Dietary interventions like gluten-free and casein-free diets have been reported to improve intestinal, autoimmune and neurological symptoms in patients with a variety of conditions; however, the underlying mechanism of benefit for such diets remains unclear. Epigenetic programming, including CpG methylation and histone modifications, occurring during early postnatal development can influence the risk of disease in later life, and such programming may be modulated by nutritional factors such as milk and wheat, especially during the transition from a solely milk-based diet to one that includes other forms of nutrition. The hydrolytic digestion of casein (a major milk protein) and gliadin (a wheat-derived protein) releases peptides with opioid activity, and in the present study, we demonstrate that these food-derived proline-rich opioid peptides modulate cysteine uptake in cultured human neuronal and gastrointestinal (GI) epithelial cells via activation of opioid receptors. Decreases in cysteine uptake were associated with changes in the intracellular antioxidant glutathione and the methyl donor S-adenosylmethionine. Bovine and human casein-derived opioid peptides increased genome-wide DNA methylation in the transcription start site region with a potency order similar to their inhibition of cysteine uptake. Altered expression of genes involved in redox and methylation homeostasis was also observed. These results illustrate the potential of milk- and wheat-derived peptides to exert antioxidant and epigenetic changes which may be particularly important during the postnatal transition from placental to GI nutrition. Differences between peptides derived from human and bovine milk may contribute to developmental differences between breastfed and formula-fed infants. Restricted antioxidant capacity, caused by wheat- and milk-derived opioid peptides, may predispose susceptible individuals to inflammation and systemic oxidation, partly explaining the benefits of gluten-free or casein-free diets.

One reason that word learning presents a challenge for children is because pairings between word forms and meanings are arbitrary conventions that children must learn via observation - e.g., the fact that "shovel" labels shovels. The present studies explore cases in which children might bypass observational learning and spontaneously infer new word meanings: By exploiting the fact that many words are flexible and systematically encode multiple, related meanings. For example, words like shovel and hammer are nouns for instruments, and verbs for activities involving those instruments. The present studies explored whether 3- to 5-year-old children possess semantic generalizations about lexical flexibility, and can use these generalizations to infer new word meanings: Upon learning that dax labels an activity involving an instrument, do children spontaneously infer that dax can also label the instrument itself? Across four studies, we show that at least by age four, children spontaneously generalize instrument-activity flexibility to new words. Together, our findings point to a powerful way in which children may build their vocabulary, by leveraging the fact that words are linked to multiple meanings in systematic ways.