Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

The cerebral hemodynamic response to phonetic changes of speech in preterm and term infants: The impact of postmenstrual age

Higher brain dysfunction, such as language delay, is a major concern among preterm infants. Cerebral substrates of cognitive development in preterm infants remain elusive, partly because of limited methods. The present study focuses on hemodynamic response patterns for brain function by using near-infrared spectroscopy. Specifically, the study investigates gestational differences in the hemodynamic response pattern evoked in response to phonetic changes of speech and cerebral hemispheric specialization of the auditory area in preterm infants (n = 60) and term infants (n = 20). Eighty neonates born between 26 and 41 weeks of gestational age (GA) were tested from 33 to 41 weeks of postmenstrual age (PMA). We analyzed the hemodynamic response pattern to phonemic and prosodic contrasts for multiple channels on temporal regions and the laterality index of the auditory area. Preterm infants younger than 39 weeks of PMA showed significantly atypical hemodynamic patterns, with an inverted response shape. Partial correlation analysis of the typicality score of hemodynamic response revealed a significant positive correlation with PMA. The laterality index of preterm infants from 39 weeks of PMA demonstrated a tendency rightward dominance for prosodic changes similar to term infants. We provide new evidence that alterations in hemodynamic regulation and the functional system for phonemic and prosodic processing in preterm infants catch up by their projected due dates. Keywords: Near-infrared spectroscopy, Preterm infants, Laterality, Speech perceptio

Validation of the Japanese Version of the Yale Food Addiction Scale 2.0 (J-YFAS 2.0)

The Yale Food Addiction Scale 2.0 (YFAS 2.0) is used for assessing food addiction (FA). Our study aimed at validating its Japanese version (J-YFAS 2.0). The subjects included 731 undergraduate students. Confirmatory factor analysis indicated the root-mean-square error of approximation, comparative fit index, Tucker–Lewis index, and standardized root-mean-square residual were 0.065, 0.904, 0.880, and 0.048, respectively, for a one-factor structure model. Kuder–Richardson α was 0.78. Prevalence of the J-YFAS 2.0-diagnosed mild, moderate, and severe FA was 1.1%, 1.2%, and 1.0%, respectively. High uncontrolled eating and emotional eating scores of the 18-item Three-Factor Eating Questionnaire (TFEQ R-18) (p < 0.001), a high Kessler Psychological Distress Scale score (p < 0.001), frequent desire to overeat (p = 0.007), and frequent snacking (p = 0.003) were associated with the J-YFAS 2.0-diagnosed FA presence. The scores demonstrated significant correlations with the J-YFAS 2.0-diagnosed FA symptom count (p < 0.01). The highest attained body mass index was associated with the J-YFAS 2.0-diagnosed FA symptom count (p = 0.026). The TFEQ R-18 cognitive restraint score was associated with the J-YFAS 2.0-diagnosed FA presence (p < 0.05) and symptom count (p < 0.001), but not with the J-YFAS 2.0-diagnosed FA severity. Like the YFAS 2.0 in other languages, the J-YFAS 2.0 has a one-factor structure and adequate convergent validity and reliability

D2 Dopamine receptor subtype mediates the inhibitory effect of dopamine on TRH-induced prolactin release from the bullfrog pituitary

International audienceDopamine receptors in mammals are known to consist of two D1-like receptors (D1 and D5) and three D2-like receptors (D2, D3 and D4). The aim of this study was to determine the dopamine receptor subtype that mediates the inhibitory action of dopamine on the release of prolactin (PRL) from the amphibian pituitary. Distal lobes of the bullfrog (Rana catesbeiana) were perifused and the amount of PRL released in the effluent medium was measured by means of a homologous enzyme-immunoassay. TRH stimulated the release of PRL from perifused pituitaries. Dopamine suppressed TRH-induced elevation of PRL release. Quinpirole (a D2 receptor agonist) also suppressed the stimulatory effect of TRH on the release of PRL, whereas SKF-38393 (a D1 receptor agonist) exhibited no such an effect. The inhibitory action of dopamine on TRH-induced PRL release from the pituitary was nullified by the addition of L-741,626 (a selective D2 receptor antagonist) to the medium, but not by the addition of SCH-23390 (a selective D1 receptor antagonist). These data indicate that the inhibitory effect of dopamine on TRH-evoked PRL release from the bullfrog pituitary gland is mediated through D2 dopamine receptors