A new strategy to build caged-compounds is presented. The approach is based on heterolytic photocleavage of a metal-ligand bond in a coordination compound. A ruthenium polypyridine complex, containing the neurocompound 4-amino pyridine (4AP) is used as the core of the phototrigger. The biomolecule is released by irradiation with visible light (>480 nm). The liberated 4AP promotes the activation of a leech neuron by means of blocking its K+ channels. The syntesis, characterization, and the inherent advantages of this method are discussed.
The ability to attribute different mental states to distinct individuals, or Theory of Mind (ToM), is widely believed to be developed mostly during preschool years. How different factors such as gender, number of siblings, or coarse personality traits affect this development is not entirely agreed upon. Here, we introduce a computerized version of the scaled ToM suite of tasks introduced by Wellman and Liu (2004), which allows us to meaningfully test ToM development on children 6 to 8-years old. We find that kids this age are still not entirely proficient in all ToM tasks, and continue to show a progression of performance with age. By testing this new age range, too, we are able to observe a significant advantage of girls over boys in ToM performance. Other factors such as number of siblings, birth order, and coarse personality traits show no significant relation with the ToM task results. Finally, we introduce a novel way to quantify the scaling property of the suite involving a sequence of set inclusions on one hand and a comparison between specially tailored sets of logistic models on the other. These measures confirm the validity of the scale in the 6- to 8-years old range.
Summary
Ionotropic γ-aminobutyric acid receptors (GABAA and GABAC) belong to the cys-loop receptor family of ligand-gated ion channels. GABAC receptors are highly expressed in the retina, mainly localized at the axon terminals of bipolar cells. Ascorbic acid, an endogenous redox agent, modulates the function of diverse proteins, and basal levels of ascorbic acid in the retina are very high. However, the effect of ascorbic acid on retinal GABA receptors has not been studied. Here we show that the function of GABAC and GABAA receptors is regulated by ascorbic acid. Patch-clamp recordings from bipolar cell terminals in goldfish retinal slices revealed that GABAC receptor-mediated currents activated by tonic background levels of extracellular GABA, and GABAC currents elicited by local GABA puffs, are both significantly enhanced by ascorbic acid. In addition, a significant rundown of GABA-puff evoked currents was observed in the absence of ascorbic acid. GABA-evoked Cl- currents mediated by homomeric ρ1 GABAC receptors expressed in Xenopus laevis oocytes were also potentiated by ascorbic acid in a concentration-dependent, stereospecific, reversible, and voltage-independent manner. Studies involving the chemical modification of sulfhydryl groups showed that the two cys-loop cysteines and histidine 141, all located in the ρ1 subunit extracellular domain, each play a key role in the modulation of GABAC receptors by ascorbic acid. Additionally, we show that retinal GABAA IPSCs and heterologously expressed GABAA receptor currents are similarly augmented by ascorbic acid. Our results suggest that ascorbic acid may act as an endogenous agent capable of potentiating GABAergic neurotransmission in the CNS.
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