N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer

Endogenous formation of N-nitroso compounds (NOCs), which are known animal carcinogens, could contribute to human carcinogenesis but definitive evidence is still lacking. To investigate the relevance of NOCs in human colorectal cancer (CRC) development, we analyzed whole genome gene expression modifications in human colon biopsies in relation to fecal NOC exposure. We had a particular interest in patients suffering from intestinal inflammation as this may stimulate endogenous NOC formation, and consequently predispose to CRC risk. Inflammatory bowel disease (IBD) patients diagnosed with ulcerative colitis and irritable bowel syndrome patients without inflammation, serving as controls, were therefore recruited. Fecal NOC were demonstrated in the majority of subjects. By associating gene expression levels of all subjects to fecal NOC levels, we identified a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may potentially induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending NOC-induced carcinogenesis. In addition, pro-inflammatory transcriptomic modifications were identified in visually non-inflamed regions of the IBD colon. However, fecal NOC levels were slightly but not significantly increased in IBD patients, suggesting that inflammation did not strongly stimulate NOC formation. We conclude that NOC exposure is associated with gene expression modifications in the human colon that may suggest a potential role of these compounds in CRC development.

Minor structural abnormalities in the infant face disrupt neural processing: a unique window into early caregiving responses

Infant faces elicit early, specific activity in the orbitofrontal cortex (OFC), a key cortical region for reward and affective processing. A test of the causal relationship between infant facial configuration and OFC activity is provided by naturally occurring disruptions to the face structure. One such disruption is cleft lip, a small change to one facial feature, shown to disrupt parenting. Using magnetoencephalography, we investigated neural responses to infant faces with cleft lip compared with typical infant and adult faces. We found activity in the right OFC at 140 ms in response to typical infant faces but diminished activity to infant faces with cleft lip or adult faces. Activity in the right fusiform face area was of similar magnitude for typical adult and infant faces but was significantly lower for infant faces with cleft lip. This is the first evidence that a minor change to the infant face can disrupt neural activity potentially implicated in caregiving.

Ratings of age of acquisition of 299 words across 25 languages: is there a cross-linguistic order of words?

We present a new set of subjective age-of-acquisition (AoA) ratings for 299 words (158 nouns, 141 verbs) in 25 languages from five language families (Afro-Asiatic: Semitic languages; Altaic: one Turkic language: Indo-European: Baltic, Celtic, Germanic, Hellenic, Slavic, and Romance languages; Niger-Congo: one Bantu language; Uralic: Finnic and Ugric languages). Adult native speakers reported the age at which they had learned each word. We present a comparison of the AoA ratings across all languages by contrasting them in pairs. This comparison shows a consistency in the orders of ratings across the 25 languages. The data were then analyzed (1) to ascertain how the demographic characteristics of the participants influenced AoA estimations and (2) to assess differences caused by the exact form of the target question (when did you learn vs. when do children learn this word); (3) to compare the ratings obtained in our study to those of previous studies; and (4) to assess the validity of our study by comparison with quasi-objective AoA norms derived from the MacArthur–Bates Communicative Development Inventories (MB-CDI). All 299 words were judged as being acquired early (mostly before the age of 6 years). AoA ratings were associated with the raters’ social or language status, but not with the raters’ age or education. Parents reported words as being learned earlier, and bilinguals reported learning them later. Estimations of the age at which children learn the words revealed significantly lower ratings of AoA. Finally, comparisons with previous AoA and MB-CDI norms support the validity of the present estimations. Our AoA ratings are available for research or other purposes.