The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA deadenylation and cell viability

The human CCR4-NOT deadenylase complex consists of at least nine enzymatic and non-enzymatic subunits. Accumulating evidence suggests that the non-enzymatic subunits are involved in the regulation of mRNA deadenylation, although their precise roles remain to be established. In this study, we addressed the function of the CNOT1 subunit by depleting its expression in HeLa cells. Flow cytometric analysis revealed that the sub G(1) fraction was increased in CNOT1-depleted cells. Virtually, the same level of the sub G1 fraction was seen when cells were treated with a mixture of siRNAs targeted against all enzymatic subunits, suggesting that CNOT1 depletion induces apoptosis by destroying the CCR4-NOT-associated deadenylase activity. Further analysis revealed that CNOT1 depletion leads to a reduction in the amount of other CCR4-NOT subunits. Importantly, the specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control cells. The formation of P-bodies, where mRNA decay is reported to take place, was largely suppressed in CNOT1-depleted cells. Therefore, CNOT1 has an important role in exhibiting enzymatic activity of the CCR4-NOT complex, and thus is critical in control of mRNA deadenylation and mRNA decay. We further showed that CNOT1 depletion enhanced CHOP mRNA levels and activated caspase-4, which is associated with endoplasmic reticulum ER stress-induced apoptosis. Taken together, CNOT1 depletion structurally and functionally deteriorates the CCR4-NOTcomplex and induces stabilization of mRNAs, which results in the increment of translation causing ER stress-mediated apoptosis. We conclude that CNOT1 contributes to cell viability by securing the activity of the CCR4-NOT deadenylase.

A Preliminary Report about a new Robot WPAL (Wearable Power-Assist Locomotor) for Paraplegic Gait Reconstruction / The Japanese Journal of Rehabilitation Medicine

To restore gait function in paraplegic patients, hip-knee-ankle-foot orthoses are available. Orthoses maintain patient stability when standing and walking by restricting the degree of freedom the lower extremity joints. The disadvantages of orthoses include difficulties in standing and sitting movements, and the large burden placed on the upper extremities in walking. Usage of orthoses in daily living was therefore restricted. We are developing a gait assist robot, which we named WPAL (Wearable Power-Assist Locomotor). WPAL has a high degree of freedom and internal power for flexion-extension direction in each hip, knee, ankle joint. We compared WPAL with the conventional Primewalk orthosis as a preliminary investigation. (1) We compared independent standing ability and walking distance of a walker in WPAL and Primewalk orthosis. All three subjects achieved an independent level in standing and walking in WPAL, despite these users requiring assistance when using the Primewalk. Walking distances with the WPAL were several times greater when compared to walking distance with the Primewalk. (2) We performed a single case study using the patient who made the most entries into WPAL exercise. We compared heart rate, physiological cost index (PCI), modified Borg scale, lateral sway of trunk in 6 minutes walking on treadmill. His heart rate, PCI, and modified Borg scale were significantly lower and lateral sway was significantly smaller in WPAL gait. WPAL which has degree of freedom and internal power in the lower extremities is considered a step toward practical powered orthoses use in gait reconstruction for spinal cord injuries.

Validating a Nutrition Support Team's (NST) Effect in Convalescent Stroke Rehabilitation using the Functional Independence Measure / The Japanese Journal of Rehabilitation Medicine

The aim of this study is to validate the effect of a nutrition support team's (NST) interventions in convalescent stroke rehabilitation using the Functional Independence Measure (FIM). Three hundred and four patients were retrospectively divided into an NST-nourishment group, an NST-losing-weight group and a non-NST group. We then compared the FIM gain, the FIM efficiency and the change of body mass index during admission among these three groups. The FIM gain was 17.3±15.9 in the NST-nourishment group and 16.7±12.5 in the non-NST group and there was no significant difference. The FIM efficiency in the NST-nourishment group (0.20±0.19) was significantly lower than the one in the non-NST group (0.27±0.19). Patients with an FIM of 53 or less showed no significant difference in FIM gain and FIM efficiency between the two groups. Since those patients who received NST intervention would tend to have a poor prognosis in general, we assumed that our “no difference” results indicated the effectiveness of the NST intervention. There was no evident relationship between FIM gains and changes in the body mass index.