AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1.

The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA + ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin in vitro and in vivo. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1.

Factors Associated With Pediatric Burn Clinic Follow-up After Emergency Department Discharge.

Attrition between emergency department discharge and outpatient follow-up is well documented across a variety of pediatric ailments. Given the importance of outpatient medical care and the lack of related research in pediatric burn populations, we examined sociodemographic factors and burn characteristics associated with outpatient follow-up adherence among pediatric burn patients. A retrospective review of medical records was conducted on patient data extracted from a burn registry database at an urban academic children's hospital over a 2-year period (January 2018-December 2019). All patients were treated in the emergency department and discharged with instructions to follow-up in an outpatient burn clinic within 1 week. A total of 196 patients (Mage = 5.5 years; 54% male) were included in analyses. Average % TBSA was 1.9 (SD = 1.5%). One third of pediatric burn patients (33%) did not attend outpatient follow-up as instructed. Older patients (odds ratio [OR] = 1.00; 95% confidence interval [CI]: [0.99-1.00], P = .045), patients with superficial burns (OR = 9.37; 95% CI: [2.50-35.16], P = .001), patients with smaller % TBSA (OR = 1.37; 95% CI: [1.07-1.76], P = .014), and patients with Medicaid insurance (OR = 0.22; 95% CI: [0.09-0.57], P = .002) or uninsured/unknown insurance (OR = 0.07; 95% CI: [0.02-0.26], P = .000) were less likely to follow up, respectively. Patient gender, race, ethnicity, and distance to clinic were not associated with follow-up. Follow-up attrition in our sample suggests a need for additional research identifying factors associated with adherence to follow-up care. Identifying factors associated with follow-up adherence is an essential step in developing targeted interventions to improve health outcomes in this at-risk population.

AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase mutant, AMPAR trafficking, long-term potentiation, and long-term depression are impaired. Overall, our data suggest that both S-nitrosylation and interactions of Thorase and NSF/PICK1 are required to modulate AMPAR-mediated synaptic plasticity. This study provides critical information that elucidates the mechanism underlying Thorase and NSF-mediated trafficking of AMPAR complexes.

Sound changes that lead to seeing longer-lasting shapes.

To survive, people must construct an accurate representation of the world around them. There is a body of research on visual scene analysis, and a largely separate literature on auditory scene analysis. The current study follows up research from the smaller literature on audiovisual scene analysis. Prior work demonstrated that when there is an abrupt size change to a moving object, observers tend to see two objects rather than one-the abrupt visual change enhances visible persistence of the briefly presented different-sized object. Moreover, if a sequence of tones accompanies the moving object, visible persistence is enhanced if the tone frequency suddenly changes at the same time that the object's size changes. Here, we show that although a sound change must occur at roughly the same time as a visual change to enhance visible persistence, there is a fairly wide time frame during which the sound change can occur. In addition, the impact of a sound change on visible persistence is not simply matter of the physical pattern: The same pattern of sound can enhance visible persistence or not, depending on how the pattern is itself perceived. Specifically, a change in a tone's frequency can enhance visible persistence when it accompanies a visual size change, but the same frequency change will not do so if the shift is embedded in a larger pattern that makes the change merely a continuation of alternating frequencies. The current study supports a scene analysis process that is both multimodal and actively constructive.