Rebecca Taylor

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy

A protein kinase links energy stores to control of autophagy. Adenosine monophosphate–activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and Caenorhabditis elegans revealed a requirement for these kinases in autophagy. In mammals, loss of AMPK or ULK1 resulted in aberrant accumulation of the autophagy adaptor p62 and defective mitophagy. Reconstitution of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation. These findings uncover a conserved biochemical mechanism coupling nutrient status with autophagy and cell survival.

Aging as an Event of Proteostasis Collapse

Aging cells accumulate damaged and misfolded proteins through a functional decline in their protein homeostasis (proteostasis) machinery, leading to reduced cellular viability and the development of protein misfolding diseases such as Alzheimers and Huntingtons. Metabolic signaling pathways that regulate the aging process, mediated by insulin/IGF-1 signaling, dietary restriction, and reduced mitochondrial function, can modulate the proteostasis machinery in many ways to maintain a youthful proteome for longer and prevent the onset of age-associated diseases. These mechanisms therefore represent potential therapeutic targets in the prevention and treatment of such pathologies.

XBP-1 Is a Cell-Nonautonomous Regulator of Stress Resistance and Longevity

The ability to ensure proteostasis is critical for maintaining proper cell function and organismal viability but is mitigated by aging. We analyzed the role of the endoplasmic reticulum unfolded protein response (UPR(ER)) in aging of C. elegans and found that age-onset loss of ER proteostasis could be reversed by expression of a constitutively active form of XBP-1, XBP-1s. Neuronally derived XBP-1s was sufficient to rescue stress resistance, increase longevity, and activate the UPR(ER) in distal, non-neuronal cell types through a cell-nonautonomous mechanism. Loss of UPR(ER) signaling components in distal cells blocked cell-nonautonomous signaling from the nervous system, thereby blocking increased longevity of the entire animal. Reduction of small clear vesicle (SCV) release blocked nonautonomous signaling downstream of xbp-1s, suggesting that the release of neurotransmitters is required for this intertissue signaling event. Our findings point toward a secreted ER stress signal (SERSS) that promotes ER stress resistance and longevity.

Analysis of aging in Caenorhabditis elegans.

This chapter is dedicated to the study of aging in Caenorhabditis elegans (C. elegans). The assays are divided into two sections. In the first section, we describe detailed protocols for performing life span analysis in solid and liquid medium. In the second section, we describe various assays for measuring age-related changes. Our laboratory has been involved in several fruitful collaborations with non-C. elegans researchers keen on testing a role for their favorite gene in modulating aging (Carrano et al., 2009; Dong et al., 2007; Raices et al., 2008; Wolff et al., 2006). But even with the guidance of trained worm biologists, this undertaking can be daunting. We hope that this chapter will serve as a worthy compendium for those researchers who may or may not have immediate access to laboratories studying C. elegans.

Food Store Choices of Poor Households: A Discrete Choice Analysis of the National Household Food Acquisition and Purchase Survey (FoodAPS)

Policymakers are pursing initiatives to increase food access for low-income households. However, due in part to previous data deficiencies, there is still little evidence supporting the assumption that improved food store access will alter dietary habits, especially for the poorest of U.S. households. This article uses the new National Household Food Acquisition and Purchase Survey (FoodAPS) to estimate consumer food outlet choices as a function of outlet type and household attributes in a multinomial mixed logit model. In particular, we allow for the composition of the local retail food environment to play a role in explaining household store choice decisions and food acquisition patterns. We find that households are willing to pay more per week in distance traveled to shop at superstores, supermarkets, and fast food outlets than at farmers markets and smaller grocery stores, and that willingness to pay is heterogeneous across income group, Supplemental Nutrition Assistance Program participation, and other household and food environment characteristics. Our results imply that policymakers should consider incentivizing the building of certain outlet types over others, and that Healthy Food Financing Initiatives should be designed to fit the sociodemographic composition of each identified low-income, low-access area in question.

Diffusion of Drip Irrigation: The Case of California

Abstract This article provides insights regarding the state of the literature on the economics of drip irrigation adoption and diffusion. Our literature review finds that the methodological approaches to studying diffusion—conceptual modeling, empirical analysis, and historical narratives—are complementary, yet historical analyses have been underemphasized. To address this gap, we conduct a historical analysis of the diffusion of drip irrigation in California. Our forty‐five‐year narrative highlights that the successful adoption of drip irrigation to diverse crops and locations required (i) coevolution of the technology and complementary production processes, and (ii) joint efforts by private and public experts at the local level.