Caveolae are invaginations of the plasma membrane involved in many cellular processes, including clathrinindependent endocytosis, cholesterol transport, and signal transduction. They are characterized by the presence of caveolin proteins. Mutations that cause deficiency in caveolin-3, which is expressed exclusively in skeletal and cardiac muscle, have been linked to muscular dystrophy. Polymerase I and transcript release factor (PTRF; also known as cavin) is a caveolar-associated protein suggested to play an essential role in the formation of caveolae and the stabilization of caveolins. Here, we identified PTRF mutations in 5 nonconsanguineous patients who presented with both generalized lipodystrophy and muscular dystrophy. Muscle hypertrophy, muscle mounding, mild metabolic complications, and elevated serum creatine kinase levels were observed in these patients. Skeletal muscle biopsies revealed chronic dystrophic changes, deficiency and mislocalization of all 3 caveolin family members, and reduction of caveolae structure. We generated expression constructs recapitulating the human mutations; upon overexpression in myoblasts, these mutations resulted in PTRF mislocalization and disrupted physical interaction with caveolins. Our data confirm that PTRF is essential for formation of caveolae and proper localization of caveolins in human cells and suggest that clinical features observed in the patients with PTRF mutations are associated with a secondary deficiency of caveolins.

If we view a visual scene that contains many objects, then momentarily close our eyes, some details persist while others seem to fade. Discrete models of visual working memory (VWM) assume that only a few items can be actively maintained in memory, beyond which pure guessing will emerge. Alternatively, continuous resource models assume that all items in a visual scene can be stored with some precision. Distinguishing between these competing models is challenging, however, as resource models that allow for stochastically variable precision (across items and trials) can produce error distributions that resemble random guessing behavior. Here, we evaluated the hypothesis that a major source of variability in VWM performance arises from systematic variation in precision across the stimuli themselves; such stimulus-specific variability can be incorporated into both discrete-capacity and variable-precision resource models. Participants viewed multiple oriented gratings, and then reported the orientation of a cued grating from memory. When modeling the overall distribution of VWM errors, we found that the variable-precision resource model outperformed the discrete model. However, VWM errors revealed a pronounced “oblique effect”, with larger errors for oblique than cardinal orientations. After this source of variability was incorporated into both models, we found that the discrete model provided a better account of VWM errors. Our results demonstrate that variable precision across the stimulus space can lead to an unwarranted advantage for resource models that assume stochastically variable precision. When these deterministic sources are adequately modeled, human working memory performance reveals evidence of a discrete capacity limit.

Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Previous studies have suggested that people can maintain prioritized items in visual working memory for many seconds, with negligible loss of information over time. Such findings imply that working memory representations are robust to the potential contaminating effects of internal noise. However, once visual information is encoded into working memory, one might expect it to inevitably begin degrading over time, as this actively maintained information is no longer tethered to the original perceptual input. Here, we examined this issue by evaluating working memory for single central presentations of an oriented grating, color patch, or face stimulus, across a range of delay periods (1, 3, 6, or 12 s). We applied a mixture-model analysis to distinguish changes in memory precision over time from changes in the frequency of outlier responses that resemble random guesses. For all 3 types of stimuli, participants exhibited a clear and consistent decline in the precision of working memory as a function of temporal delay, as well as a modest increase in guessing-related responses for colored patches and face stimuli. We observed a similar loss of precision over time while controlling for temporal distinctiveness. Our results demonstrate that visual working memory is far from lossless: while basic visual features and complex objects can be maintained in a quite stable manner over time, these representations are still subject to noise accumulation and complete termination. (PsycINFO Database Record

A prevalent view of visual working memory (VWM) is that visual information is actively maintained in the form of perceptually integrated objects. Such reliance on object-based representations would predict that after an object is fully encoded into VWM, all features of that object would need to be maintained as a coherent unit. Here, we evaluated this idea by testing whether memory resources can be redeployed to a specific feature of an object already stored in VWM. We found that observers can utilize a retrospective cue presented during the maintenance period to attenuate both the gradual deterioration and complete loss of memory for a cued feature over time, but at the cost of accelerated loss of information regarding the uncued feature. Our findings demonstrate that object representations held within VWM can be decomposed into individual features, and that having to retain additional features imposes greater demands on active maintenance processes.