For Whom, and for What, is Experience Sampling More Accurate Than Retrospective Report?

The experience sampling method (ESM) is often used in research, and promoted for clinical use, with the rationale that it avoids problematic inaccuracies and biases that attend retrospective measures of mental phenomena. Research suggests that averaged scores from ESM data are more accurate than retrospective ratings. However, it is not known how well individuals can remember information about momentary (rather than averaged) mental states, nor how accurately they estimate the dynamic covariation of these states. Individual differences in retrospective accuracy are also poorly understood. In two pre-registered studies, we examined differences between retrospective memory for stress and self-esteem and data gathered via experience sampling and examined whether alexithymia predicted accuracy. Results of both studies revealed substantial discrepancies between retrospective ratings and ESM ratings, especially for momentary states and their covariation. Alexithymia was positively related to recognition of stress means and variability but unrelated to recall of either stress or self-esteem, their variability, or their covariation. These findings suggest that experience sampling may be more useful than self-report when precise information is needed about the timing of mental states and dynamics among them

AChBP-targeted α-conotoxin correlates distinct binding orientations with nAChR subtype selectivity

Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel α-conotoxin (α-TxIA) in the venom of Conus textile. α-TxIA bound with high affinity to AChBPs from different species and selectively targeted the α3β2 nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20° backbone tilt compared to other AChBP–conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases