Organelle transporters define metabolic compartmentalization, and how this metabolite transport process can be modulated is poorly explored. Here, we discovered that human SLC25A39, a mitochondrial transporter critical for mitochondrial glutathione uptake, is a short-lived protein under dual regulation at the protein level. Co-immunoprecipitation mass spectrometry and CRISPR knockout (KO) in mammalian cells identified that mitochondrial m-AAA protease AFG3L2 is responsible for degrading SLC25A39 through the matrix loop 1.
View Article and Find Full Text PDFWe present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling.
View Article and Find Full Text PDFWhat drives consumer activism during trade disputes? We investigate this important and timely question using a survey experiment in the context of the recent Canada-US trade dispute. We find that Canadians are more likely to express willingness to take punitive actions in the form of boycotting during a trade conflict when they learn that Americans are taking such actions (retaliation), when many fellow citizens are taking such actions (peer pressure), and when they are rallied by their government (elite cue). Among the three conditions, peer pressure has the largest effect.
View Article and Find Full Text PDFHow do authoritarian states organize their coercive institutions over space? We argue that autocrats maximize the utility of their limited coercive resources by clustering them with perceived threats in society, i.e., segments of the population that are ideologically distant and have mobilizational potential.
View Article and Find Full Text PDFBackground: Most conditions in orthopaedic surgery are preference-sensitive, where treatment choices are based on the patient's values and preferences. One set of tools increasingly used to help align treatment choices with patient preferences are question prompt lists (QPLs), which are comprehensive lists of potential questions that patients can ask their physicians during their encounters. Whether or not a comprehensive orthopaedic-specific question prompt list would increase patient-perceived involvement in care more effectively than might three generic questions (the AskShareKnow questions) remains unknown; learning the answer would be useful, since a three-question list is easier to use compared with the much lengthier QPLs.
View Article and Find Full Text PDFSynthetic biological systems are currently created by an ad hoc, iterative process of design, simulation, and assembly. These systems would greatly benefit from the introduction of a more formalized and rigorous specification of the desired system components as well as constraints on their composition. In order to do so, the creation of robust and efficient design flows and tools is imperative.
View Article and Find Full Text PDFBackground: Synthetic biological systems are currently created by an ad-hoc, iterative process of specification, design, and assembly. These systems would greatly benefit from a more formalized and rigorous specification of the desired system components as well as constraints on their composition. Therefore, the creation of robust and efficient design flows and tools is imperative.
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