A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B

Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316. Phosphorylation at this residue results in inhibition of its catalytic activity in vitro and in vivo. On the other hand, phosphatase PP2A-PP2R3B can remove this inhibitory phosphorylation. We propose that the opposing activities of ULK1-mediated phosphorylation and PP2A-mediated dephosphorylation provide a phospho-switch that regulates the cellular activity of ATG4B to control LC3 processing

Latent variables and route choice behavior

In the last decade, a broad array of disciplines has shown a general interest in enhancing discrete choice models by considering the incorporation of psychological factors affecting decision making. This paper provides insight into the comprehension of the determinants of route choice behavior by proposing and estimating a hybrid model that integrates latent variable and route choice models. Data contain information about latent variable indicators and chosen routes of travelers driving regularly from home to work in an urban network. Choice sets include alternative routes generated with a branch and bound algorithm. A hybrid model consists of measurement equations, which relate latent variables to measurement indicators and utilities to choice indicators, and structural equations, which link travelers' observable characteristics to latent variables and explanatory variables to utilities. Estimation results illustrate that considering latent variables (i.e., memory, habit, familiarity, spatial ability, time saving skills) alongside traditional variables (e.g., travel time, distance, congestion level) enriches the comprehension of route choice behavior

Impact of integrated multimodal traveler information on auto commuter's mode switching propensity

Aim: Real-time traveler information affects auto commuter’s travel behavior. Method: An ordered probit model is used to analyze auto commuter’s mode switching propensity under influence of simulated real-time multimodal traveler information. A travel preference survey is administered to car drivers to gather individual commuter’s travel decisions under integrated multimodal traveler information. Result: It is shown that integrated multimodal traveler information can influence willingness of car drivers to switch mode of travel, while socio-economic characteristics also influence the mode choice decision

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Mild everyday altered states of consciousness

This thesis presents an ethnographic study of altered states of consciousness (ASCs). Such states have been of interest to some writers in social anthropology (Turner 1992, Bourguignon 1989) and in some areas of psychology, especially transpersonal psychology (Beischel et al 2011:114, Vaughan 1993:160). But these literatures reveal a focus on rather extreme experiences not found in everyday life. There has been very little interest in milder altered states which are very common in our experience. These became the focus of the project. A literature review begins with an appraisal of writing in mainstream psychology on consciousness. A lack of study of ASCs is identified. The work of William James is reviewed as an important theorist for this thesis in his study of consciousness, particularly his 'stream of consciousness' (James 1950:239). James is seen to form a bridge between mainstream psychology and the development of trans personal psychology, a central theoretical perspective for this thesis. The development ofthe transpersonal psychology movement is explored. The transpersonal concerns 'those experiences which allegedly enable the individual to see beyond the conditioned ego and to identify some deeper and more enduring sense of self (Fontana & Slack 2005:7). The work of Maslow, Stanislav Grof and James is reviewed, particularly James's work on mystical states (James 1982, 1911). Key theoretical issues are identified: the problem of belief, universalism/relativism debates, validity of spiritual experience, and the 'participatory' in the work of Jorge Ferrer. Transpersonal anthropology is a sister movement and forms the second key theoretical perspective. Anthropological study of religion and spiritual beliefs and practices is traced through its early history in the work of Lucien Levy-Bruhl and Emile Durkheim. The Literary Turn in anthropology and also the participatory as a method are seen to open up the study of trans personal experience on its own terms. The work of Victor and Edith Turner forms a key reference point in this review. Key issues explored in transpersonal psychology are revisited here. A short consideration of literature on ASCs as healing is also presented, as well as literatures specific to each group studied. The methodology used draws on theoretical and practical debates around dialogic anthropology, and also participant observation. The history and development of ethnography is explored, particularly the 'Writing Culture' debates. Ethnographic fieldwork was carried out over a period of three years. Groups of individuals were chosen whose activities were ASC-inducing. These were members of a Hindu temple and a Lubavitch Jewish synagogue, members of a sport training group, users of a local forest , a musical instrument-maker group who were also musicians, and various excessive viewers of television. Fieldwork revealed patterns and types of ASCs, many of which are not found in the literature: absorbed, daydream and transcendent types; mindful/mindless ASCs; 'top-up' ASCs; a sport triple ASC; a total 'Lifeworld' ASC, a dialogue between positive and negative ASCs, and ASCs reaching beyond the self. The therapeutic value of these are highlighted in the lives of participants. Wider patterns are also discussed, such as sacred experience in secular contexts, collective ASCs and 'communitas' (Turner 2012), and challenges to boundaries of so-called 'reality out there' and fantasy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Car drivers' compliance with route advice and willingness to choose socially desirable routes

This study describes the results of a stated choice experiment conducted to analyze route choice behavior of car drivers under influence of advice and feedback on environmental consequences of their trips. Framing of the route advice is varied in terms of goal of the agency providing the advice (system or individual optimality) and extent to which it is generic or tailored to the specific preferences of the person. The findings suggest that, under conditions of rich information about attributes of choice alternatives, advice is discarded when it is supposed to serve the driver’s own interests and information allows the individuals to evaluate outcomes independently, but is taken into account when it is said to serve traffic management objectives. In line with expectations, the impact of advice is larger when it is labeled as personal compared to when it is labeled as generic. An interesting finding is that the impact of advice on evaluations of route alternatives is not uniform across attributes. Whereas some attributes become suppressed in the evaluation, others become more salient. The study further provides evidence that travelers are willing to trade-off social objectives against individual-level objectives. The authors discuss the implications of these findings for the design and use of travel information systems as an instrument for traffic management and identify problems for future research