Dynamics of infant habituation: infants' discrimination of musical excerpts.

Schöner and Thelen (2006) summarized the results of many habituation studies as a set of generalizations about the emergence of novelty preferences in infancy. One is that novelty preferences emerge after fewer trials for older than for younger infants. Yet in habituation studies using an infant-controlled procedure, the standard criterion of habituation is a 50% decrement in looking regardless of he ages of the participants. If younger infants require more looking to habituate than do older infants, it might follow that novelty preferences will emerge for younger infants when a more stringent criterion is imposed, e.g., a 70% decrement in looking. Our earlier investigation of infants' discrimination of musical excerpts provides a basis and an opportunity for assessing this idea. Flom et al. (2008) found that 9-month-olds, but not younger infants, unambiguously discriminate "happy" and "sad" musical excerpts. The purpose of the current study was to examine younger infants' discrimination of happy and sad musical excerpts using a more stringent, 70% habituation criterion. In Experiment 1, 5- and 7-month olds were habituated to three musical excerpts rated as happy or sad. Following habituation infants were presented with two musical excerpts from the other affect group. Infants at both ages showed significant discrimination. In Experiment 2, 5- and 7-month-olds were presented with two new excerpts from the same affective group as the habituation excerpts. The infants did not discriminate these novel, yet affectively similar excerpts. In Experiment 3, 5- and 7-month-olds discriminated individual happy and sad excerpts. These results replicate those for the older, 9-month-olds in the previous investigation. The results are important as they demonstrate that whether infants show discrimination using an infant-controlled procedure is affected by the researchers' chosen criterion of habituation.

Structure-activity relationships of flavonoids as inhibitors of breast cancer resistance protein (BCRP).

Flavonoids are an interesting group of natural products ubiquitously present in human diet. Their consumption has been associated with various and differing beneficial health effects. However, several flavonoids have been reported to inhibit the breast cancer resistance protein (BCRP) encoded by the ABCG2 gene. Thus, the consumption of flavonoids with high inhibitory activity could change pharmacokinetics and drug levels of drugs that are BCRP substrates. In cancer patients receiving chemotherapy an increased intake of such flavonoids could lead to adverse effects. We investigated a structurally diverse set of flavonoids, including derivatives with a rare C-methylated structure that were isolated from plants used in traditional medicine. The flavones retusin and ayanin were found to be highly potent inhibitors of BCRP, showing only slightly less potency than Ko143, the most potent ABCG2 inhibitor known so far. The activity data were analyzed by 2D and 3D QSAR analyses and the results revealed the impact of the different substituents at the various positions of the flavonoid core on activity. Additionally, a lateral 2D QSAR analysis of data collected from the literature was performed aiming to derive more general information about the influence of distinct structural features on the inhibitory potency of flavonoids. The comparative QSAR analyses led to a consistent picture of the effects of the different substituents at various positions of the flavone backbone. The following structural features were found to contribute positively to BCRP inhibition: a hydroxyl group in position 5, double bond between position 2 and 3, and a methoxy group in position 3. The exchange of a 3-methoxy group by an OH-group acting also as a hydrogen bond donor, resulted in decrease in activity underlining the potential role of the hydrogen bond acceptor 3-OCH(3) for the interaction with BCRP.

Structure-activity relationships of new inhibitors of breast cancer resistance protein (ABCG2).

At the end of the last century tariquidar (XR9576) was synthesized, pharmacologically investigated, and classified as a promising 3rd generation P-glycoprotein (P-gp) modulator. Following the discovery of BCRP in 1998 an increasing number of substances were studied in relation to their potency to interact with this transporter. Recently it has been shown that XR9576 inhibits both P-gp and BCRP transport function similarly to GF120918 (elacridar). This observation prompted us to investigate 5 XR compounds and 25 structurally related derivatives synthesized in our laboratory for their BCRP inhibitory effect. The biological activity data were determined by our new Hoechst 33342 assay that has been transferred from P-gp to BCRP overexpressing cells. 3D-QSAR models (CoMFA and CoMSIA) were generated and validated by the leave-many-out method and the scrambling stability test. The best models yielded an internal predictive squared correlation coefficient higher than 0.8 and contained steric, electrostatic, hydrophobic, and hydrogen bond donor fields. To our knowledge, this is the first 3D-QSAR analysis of BCRP inhibitors. Additionally the biological activity data determined in P-gp overexpressing cells on one side and BCRP overexpressing cells on the other side were compared to identify selective and non-selective inhibitors of P-gp and BCRP. The results may help to get a better insight which structural elements are necessary to direct the interaction of these compounds with P-gp and/or BCRP.

Infants' discrimination of happy and sad music.

Infants can detect information specifying affect in infant- and adult-directed speech, familiar and unfamiliar facial expressions, and in point-light displays of facial expressions. We examined 3-, 5-, 7-, and 9-month-olds' discrimination of musical excerpts judged by adults and preschoolers as happy and sad. In Experiment 1, using an infant-controlled habituation procedure, 3-, 5-, 7-, and 9-month-olds heard three musical excerpts that were rated as either happy or sad. Following habituation, infants were presented with two new musical excerpts from the other affect group. Nine-month-olds discriminated the musical excerpts rated as affectively different. Five- and seven-month-olds discriminated the happy and sad excerpts when they were habituated to sad excerpts but not when they were habituated to happy excerpts. Three-month-olds showed no evidence of discriminating the sad and happy excerpts. In Experiment 2, 5-, 7-, and 9-month-olds were presented with two new musical excerpts from the same affective group as the habituation excerpts. At no age did infants discriminate these novel, yet affectively similar, musical excerpts. In Experiment 3, we examined 5-, 7-, and 9-month-olds' discrimination of individual excerpts rated as affectively similar. Only the 9-month-olds discriminated the affectively similar individual excerpts. Results are discussed in terms of infants' ability to discriminate affect across a variety of events and its relevance for later social-communicative development.