All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers

Alzheimer’s disease (AD) is the most common type of senile dementia in aging populations. Amyloid β (Aβ)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aβ-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aβ binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aβ effects even in the absence of receptor–peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aβ isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known blocker of l-Aβ isomer channels. MD simulations further verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism

Plasma prolactin variations and cyclic ovarian activity in ewes submitted to different light regimens

International audienc

Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants

OBJECTIVE—To develop and validate a scale suitable for use in clinical practice as a tool for assessing prolonged pain in premature infants.
METHODS—Pain indicators identified by observation of preterm infants and selected by a panel of experts were used to develop the EDIN scale (Échelle Douleur Inconfort Nouveau-Né, neonatal pain and discomfort scale). A cohort of preterm infants was studied prospectively to determine construct validity, inter-rater reliability, and internal consistency of the scale.
RESULTS—The EDIN scale uses five behavioural indicators of prolonged pain: facial activity, body movements, quality of sleep, quality of contact with nurses, and consolability. The validation study included 76 preterm infants with a mean gestational age of 31.5weeks. Inter-rater reliability was acceptable, with a κ coefficient range of 0.59-0.74. Internal consistency was high: Cronbach's α coefficients calculated after deleting each item ranged from 0.86 to 0.94. To establish construct validity, EDIN scores in two extreme situations (pain and no pain) were compared, and a significant difference was observed.
CONCLUSIONS—The validation data suggest that the EDIN is appropriate for assessing prolonged pain in preterm infants. Further studies are warranted to obtain further evidence of construct validity by comparing scores in less extreme situations.


Relations mere-jeune et reponse prolactinique a la stimulation mammaire chez la vache : influences de la traite et de l'allaitement libre ou entrave

National audienc

Relations mere-jeune et reponse prolactinique a la stimulation mammaire chez la vache : influences de la traite et de l'allaitement libre ou entrave

National audienc