A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.

The intersection of the amyloid cascade hypothesis and the implication of metal ions in Alzheimer's disease progression has sparked an interest in using metal-binding compounds as potential therapeutic agents. In the present work, we describe a prochelator SWH that is enzymatically activated by beta-secretase to produce a high affinity copper chelator CP. Because beta-secretase is responsible for the amyloidogenic processing of the amyloid precursor protein, this prochelator strategy imparts disease specificity toward copper chelation not possible with general metal chelators. Furthermore, once activated, CP efficiently sequesters copper from amyloid-beta, prevents and disassembles copper-induced amyloid-beta aggregation, and diminishes copper-promoted reactive oxygen species formation.

Autobiographical Memories for Very Negative Events: The Effects of Thinking about and Rating Memories.

In three related experiments, 250 participants rated properties of their autobiographical memory of a very negative event before and after writing about either their deepest thoughts and emotions of the event or a control topic. Levels of emotional intensity of the event, distress associated with the event, intrusive symptoms, and other phenomenological memory properties decreased over the course of the experiment, but did not differ by writing condition. We argue that the act of answering our extensive questions about a very negative event led to the decrease, thereby masking the effects of expressive writing. To show that the changes could not be explained by the mere passage of time, we replicated our findings in a fourth experiment in which all 208 participants nominated a very negative event, but only half the participants rated properties of their memory in the first session. Implications for reducing the effects of negative autobiographical memories are discussed.

The Effect of Reputation Shocks to Rating Agencies on Corporate Disclosures

This paper explores the effect of credit rating agency’s (CRA) reputation on the discretionary disclosures of corporate bond issuers. Academics, practitioners, and regulators disagree on the informational role played by major CRAs and the usefulness of credit ratings in influencing investors’ perception of the credit risk of bond issuers. Using management earnings forecasts as a measure of discretionary disclosure, I find that investors demand more (less) disclosure from bond issuers when the ratings become less (more) credible. In addition, using content analytics, I find that bond issuers disclose more qualitative information during periods of low CRA reputation to aid investors better assess credit risk. That the corporate managers alter their voluntary disclosure in response to CRA reputation shocks is consistent with credit ratings providing incremental information to investors and reducing adverse selection in lending markets. Overall, my findings suggest that managers rely on voluntary disclosure as a credible mechanism to reduce information asymmetry in bond markets.