Background and Purpose-Constraint-induced movement therapy (CI therapy) has previously been shown to produce large improvements in actual amount of use of a more affected upper extremity in the "real-world" environment in patients with chronic stroke (ie, Ͼ1 year after the event). This work was carried out in an American laboratory. Our aim was to determine whether these results could be replicated in another laboratory located in Germany, operating within the context of a healthcare system in which administration of conventional types of physical therapy is generally more extensive than in the United States. Methods-Fifteen chronic stroke patients were given CI therapy, involving restriction of movement of the intact upper extremity by placing it in a sling for 90% of waking hours for 12 days and training (by shaping) of the more affected extremity for 7 hours on the 8 weekdays during that period. Results-Patients showed a significant and very large degree of improvement from before to after treatment on a laboratory motor test and on a test assessing amount of use of the affected extremity in activities of daily living in the life setting (effect sizes, 0.9 and 2.2, respectively), with no decrement in performance at 6-month follow-up. During a pretreatment control test-retest interval, there were no significant changes on these tests. Conclusions-Results replicate in Germany the findings with CI therapy in an American laboratory, suggesting that the intervention has general applicability. (Stroke. 1999;30:586-592.)
Language ability and handedness are likely to be associated with asymmetry of the cerebral cortex (grey matter) and connectivity (white matter). Grey matter asymmetry, most likely linked to language has been identified with voxel-based morphometry (VBM) using T(1)-weighted images. Differences in white matter obtained with this technique are less consistent, probably due to the relative insensitivity of the T(1) contrast to the ultrastructure of white matter. Furthermore, previous VBM studies failed to find differences related to handedness in either grey or white matter. We revisited these issues and investigated two independent groups of subjects with diffusion-tensor imaging (DTI) for asymmetries in white matter composition. Using voxel-based statistical analyses an asymmetry of the arcuate fascicle was observed, with higher fractional anisotropy in the left hemisphere. In addition, we show differences related to handedness in the white matter underneath the precentral gyrus contralateral to the dominant hand. Remarkably, these findings were very robust, even when investigating small groups of subjects. This highlights the sensitivity of DTI for white matter tissue differences, making it an ideal tool to study small patient populations.
Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins and initiate G-protein-independent signalling. Arrestins have a bi-lobed structure that is stabilized by a long carboxy-terminal tail (C-tail), and displacement of the C-tail by receptor-attached phosphates activates arrestins for binding active GPCRs. Structures of the inactive state of arrestin are available, but it is not known how C-tail displacement activates arrestin for receptor coupling. Here we present a 3.0 Å crystal structure of the bovine arrestin-1 splice variant p44, in which the activation step is mimicked by C-tail truncation. The structure of this pre-activated arrestin is profoundly different from the basal state and gives insight into the activation mechanism. p44 displays breakage of the central polar core and other interlobe hydrogen-bond networks, leading to a ∼21° rotation of the two lobes as compared to basal arrestin-1. Rearrangements in key receptor-binding loops in the central crest region include the finger loop, loop 139 (refs 8, 10, 11) and the sequence Asp 296-Asn 305 (or gate loop), here identified as controlling the polar core. We verified the role of these conformational alterations in arrestin activation and receptor binding by site-directed fluorescence spectroscopy. The data indicate a mechanism for arrestin activation in which C-tail displacement releases critical central-crest loops from restricted to extended receptor-interacting conformations. In parallel, increased flexibility between the two lobes facilitates a proper fitting of arrestin to the active receptor surface. Our results provide a snapshot of an arrestin ready to bind the active receptor, and give an insight into the role of naturally occurring truncated arrestins in the visual system.
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