Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism.

Evaluation of a soft exosuit designed to reduce metabolic requirements during walking.

Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL͞Wld S . Ubiquitin fusion degradation protein 2 (Ufd2) and a previously undescribed gene, D4Cole1e, span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units in Wld S . The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2, the C-terminal 302 amino acids of D4Cole1e, and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically in Wld S brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate for Wld. The third gene altered by the triplication, Rbp7, is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript in Wld S mice. However, it is undetectable on Northern blots of Wld S brain and seems unlikely to be the Wld gene. These data reveal both a candidate gene for Wld and the potential of the Wld S mutant for studies of ubiquitin and retinoid metabolism.

BackgroundSpinal cord injury is a devastating condition that can dramatically impact hand motor function. Passive and active assistive devices are becoming more commonly used to enhance lost hand strength and dexterity. Soft robotics is an emerging discipline that combines the classical principles of robotics with soft materials and could provide a new class of active assistive devices. Soft robotic assistive devices enable a human-robot interaction facilitated by compliant and light-weight structures. The scope of this work was to demonstrate that a fabric-based soft robotic glove can effectively assist participants affected by spinal cord injury in manipulating objects encountered in daily living.MethodsThe Toronto Rehabilitation Institute Hand Function Test was administered to 9 participants with C4-C7 spinal cord injuries to assess the functionality of the soft robotic glove. The test included object manipulation tasks commonly encountered during activities of daily living (ADL) and lift force measurements. The test was administered to each participant twice; once without the assistive glove to provide baseline data and once while wearing the assistive glove. The object manipulation subtests were evaluated using a linear mixed model, including interaction effects of variables such as time since injury. The lift force measures were separately evaluated using the Wilcoxon signed-rank test.ResultsThe soft robotic glove improved object manipulation in ADL tasks. The difference in mean scores between baseline and assisted conditions was significant across all participants and for all manipulated objects. An improvement of 33.42 ± 15.43% relative to the maximal test score indicates that the glove sufficiently enhances hand function during ADL tasks. Moreover, lift force also increased when using the assistive soft robotic glove, further demonstrating the effectiveness of the device in assisting hand function.ConclusionsThe results gathered in this study validate our fabric-based soft robotic glove as an effective device to assist hand function in individuals who have suffered upper limb paralysis following a spinal cord injury.Electronic supplementary materialThe online version of this article (10.1186/s12984-018-0391-x) contains supplementary material, which is available to authorized users.