A novel retinoic acid-response element requires an enhancer element mediator for transcriptional activation.

The Col11a2 gene codes for alpha2(XI), a subunit of type XI collagen that is a critical component of the cartilage extracellular matrix. The 5' regulatory region of Col11a2 was subjected to deletional analysis to detect any regulatory element in addition to the two known chondrocyte-specific enhancer elements B/C and D/E. Deletion of the region from -342 to -242 bp reduced transcriptional activity to less than 50% of wild-type, but the sequence showed no independent ability to increase transcription from a minimal promoter. When cloned downstream of the D/E enhancer, however, a subsection of the sequence nearly doubled transcriptional activity and produced an additional 3-fold activation in response to RA (retinoic acid). A 6-bp direct repeat, separated by 4 bp (a DR-4 element) near the 5'-end of this region, was found to be essential for its activity, and was further shown to bind the RA X receptor beta in electrophoretic mobility-shift assays. The present study has revealed a novel RA-response element in Col11a2 that does not interact directly with the promoter, but instead requires the D/E enhancer to mediate transcriptional activation. Proteins bound at the enhancer, therefore, would be expected to affect the transcriptional response to RA. Such a system of regulation, particularly if found to be operating in other cartilage genes, could explain the conflicting responses RA produces in chondrocytes under different experimental conditions.

The efficacy of Wii-based Movement Therapy for upper limb rehabilitation in the chronic poststroke period: a randomized controlled trial.

BACKGROUND: More effective and efficient rehabilitation is urgently needed to address the prevalence of unmet rehabilitation needs after stroke. This study compared the efficacy of two poststroke upper limb therapy protocols. AIMS AND/OR HYPOTHESIS: We tested the hypothesis that Wii-based movement therapy would be as effective as modified constraint-induced movement therapy for post-stroke upper-limb motor rehabilitation. METHODS: Forty-one patients, 2-46 months poststroke, completed a 14-day program of Wii-based Movement Therapy or modified Constraint-induced Movement Therapy in a dose-matched, assessor-blinded randomized controlled trial, conducted in a research institute or patient's homes. Primary outcome measures were the Wolf Motor Function Test timed-tasks and Motor Activity Log Quality of Movement scale. Patients were assessed at prebaseline (14 days pretherapy), baseline, post-therapy, and six-month follow-up. Data were analyzed using linear mixed models and repeated measures analysis of variance. RESULTS: There were no differences between groups for either primary outcome at any time point. Motor function was stable between prebaseline and baseline (P > 0·05), improved with therapy (P < 0·001); and improvements were maintained at six-months (P > 0·05). Wolf Motor Function Test timed-tasks log times improved from 2·1 ± 0·22 to 1·7 ± 0·22 s after Wii-based Movement Therapy, and 2·6 ± 0·23 to 2·3 ± 0·24 s after modified Constraint-induced Movement Therapy. Motor Activity Log Quality of Movement scale scores improved from 67·7 ± 6·07 to 102·4 ± 6·48 after Wii-based Movement Therapy and 64·1 ± 7·30 to 93·0 ± 5·95 after modified Constraint-induced Movement Therapy (mean ± standard error of the mean). Patient preference, acceptance, and continued engagement were higher for Wii-based Movement Therapy than modified Constraint-induced Movement Therapy. CONCLUSIONS: This study demonstrates that Wii-based Movement Therapy is an effective upper limb rehabilitation poststroke with high patient compliance. It is as effective as modified Constraint-induced Movement Therapy for improving more affected upper limb movement and increased independence in activities of daily living.