Highlighting Unseen Activity Through 48-Hour Continuous Measurement in Subacute Stroke Rehabilitation: Preliminary Cohort Study.

Background: Motor impairments not only lead to a significant reduction in patient activity levels but also trigger a further deterioration in motor function due to deconditioning, which is an issue that is particularly pronounced during hospitalization. This deconditioning can be countered by sustaining appropriate activity levels. Activities that occur outside of scheduled programs, often overlooked, are critical in this context.

Immediate Reduction in Spasticity of Ankle Plantar Flexors in a Stroke Patient after Treatment with a Spinning Permanent Magnet Device.

Background: Magnetic stimulation devices can be large because of the need for cooling systems. We developed a compact and lightweight Spinning Permanent Magnet (SPM) device that generates magnetic fields with intensities below the motor threshold. In this report, we present the case of a post-stroke patient in which an immediate reduction in spasticity of the ankle plantar flexors was achieved after SPM treatment.

Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis.

During cytokinesis, the central spindle, a bundle of interdigitated anti-parallel microtubules between separating chromosomes, recruits various cytokinetic regulator proteins to the cleavage region. Here, we show that the level of protein ubiquitylation is strikingly and transiently elevated in Aurora B kinase-positive double-band regions of the central spindle during cytokinesis. Two deubiquitylating enzymes UBPY and AMSH, which act on endosomes in interphase, were also recruited to the cleavage region.

14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase.

The deubiquitinating enzyme UBPY, also known as USP8, regulates cargo sorting and membrane traffic at early endosomes. Here we demonstrate the regulatory mechanism of the UBPY catalytic activity. We identified 14-3-3 epsilon, gamma, and zeta as UBPY-binding proteins using co-immunoprecipitation followed by mass spectrometric analysis.

A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes.

Monoubiquitination of endocytosed cell surface receptors serves as a sorting signal for their trafficking from endosomes to lysosomes. The sorting of ubiquitinated proteins is executed by concerted actions of class E vacuolar protein sorting (Vps) proteins. Some proteins in the sorting machinery undergo monoubiquitination, suggesting that their functions are also regulated by ubiquitination.

Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes.

Ligand-activated receptor tyrosine kinases undergo endocytosis and are transported via endosomes to lysosomes for degradation. This "receptor down-regulation" process is crucial to terminate the cell proliferation signals produced by activated receptors. During the process, ubiquitination of the receptors serves as a sorting signal for their trafficking from endosomes to lysosomes.

A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor.

Ligand-stimulated growth factor receptors are rapidly internalized and transported to early endosomes. Unstimulated receptors are also internalized constitutively, although at a slower rate, and delivered to the same organelle. At early endosomes, stimulated receptors are sorted for the lysosomal degradation pathway, whereas unstimulated receptors are mostly recycled back to the cell surface.

Association with Hrs is required for the early endosomal localization, stability, and function of STAM.

Members of the STAM family of proteins, STAM1 and STAM2, are associated with Hrs through their coiled-coil regions. Both Hrs and STAM bind ubiquitin and are involved in endosomal sorting of ubiquitinated cargo proteins for trafficking to the lysosome. Here we examined the biological significance of STAM binding to Hrs.

STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif.

Conjugation with ubiquitin acts as a sorting signal for proteins in the endocytic and biosynthetic pathways at the endosome. Signal-transducing adaptor molecule (STAM) proteins, STAM1 and STAM2, are associated with hepatocyte growth factor-regulated substrate (Hrs) but their function remains unknown. Herein, we show that STAM proteins bind ubiquitin and ubiquitinated proteins and that the tandemly located VHS (Vps27/Hrs/STAM) domain and ubiquitin-interacting motif serve as the binding site(s).