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Disorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.

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Using novel monthly survey data from 1993-2012 on small business managerial perceptions of financial constraints, we address three questions regarding comparative advantages of small banks in alleviating such constraints. 1) Do small banks (still) have these comparative advantages? YES. 2) Do these advantages change over time? YES. They become greater during adverse economic conditions. 3) Do small banks have comparative advantages in providing liquidity insurance to the customers of large banks experiencing liquidity shocks during financial crises? YES. Our findings suggest significant social costs from bank consolidation over time to be weighed against the social benefits.

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This study shows that weather-based indicators of mood impact perceptions of mispricing and trading decisions of institutional investors. We use survey and disaggregated trade data to show that relatively cloudier days increase perceived overpricing in both individual stocks and the Dow Jones Industrial Index, and increases selling propensities of institutions. We introduce stock-level measures of investor mood, and demonstrate that investor pessimism negatively impacts daily stock returns, mostly among stocks that are costly to arbitrage. Finally, we document comovement in stocks experiencing similar changes in investor mood. These findings complement existing studies on the weather effect on stock index returns, and identify an additional channel through which it can manifest.