The ubiquitin hybrid genes Uba80 and Uba52 encode ubiquitin (Ub), which is fused to the ribosomal proteins S27a (RPS27a) and L40 (RPL40), respectively. Here, we show that these genes are preferentially over-expressed during hepatoma cell apoptosis. Experiments using the tet-inducible transgenic system revealed that over-expression of the ubiquitin hybrid genes sensitized the cells to apoptosis. Further analysis suggested that Ub, and not RPS27a or RPL40, was associated with apoptotic cell death. Cleavage-resistant mutation analysis revealed that the N-terminal portion and the last two amino acids (GG) of Ub are critical for cleavage at the junction between the two protein moieties. An apoptogenic stimulus enhances the nuclear targeting and aggregation of Ub in the nucleus, resulting in histone H2A deubiquitylation followed by abnormal ubiquitylation of the nuclear envelope and the lamina. These events accompany the apoptotic nuclear morphology in the late stage of apoptosis. Each fused RP is localized in the nucleoli. These results suggest a role for Ub hybrid proteins in the altered nuclear dynamics of Ub during tumor cell apoptosis induced by apoptogenic stimuli.
This study evaluated plantar pressure distribution and its clinical significance in patients with diabetic foot toe deformities. Patients with diabetic claw or hammer toe deformities (patient group; n = 30) and healthy subjects without toe deformities (control group; n = 30) were recruited into the study. Plantar pressures in different regions of the foot were measured using the F-scan ® in-shoe plantar pressure dynamic analysis system. Peak pressures in the hallux and first to fifth metatarsal heads were significantly higher in the patient group compared with the control group. In the midfoot there was no significant difference between the two groups. Hindfoot peak plantar pressures were significantly lower in the patient group compared with the control group. The results indicated that toe deformities in patients with diabetes increased forefoot plantar pressures to abnormally high levels. If plantar pressure is regularly monitored in patients with diabetic foot, toe deformities might be detected earlier and ulceration prevented.
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