Mouse RNA polymerase I (Pol I) has, besides its 11 bona fide subunits, three polymerase associated factors, termed PAF53, 51 and 49 with respect to the size of each molecule. In order to analyze the function of PAFs, cDNA encoding PAF53 was isolated using an oligonucleotide probe derived from an oligopeptide sequence. The cDNA of PAF53 predicts a polypeptide of 434 amino acids with a sequence similarity to yeast Pol 1 49 kDa subunit. Anti‐PAF53 antibody does not block the random transcription activity of Pol I, but blocks specific transcription from mouse ribosomal RNA promoter, demonstrating the requirement of PAF53 in the accurate initiation of Pol I transcription. Moreover, PAF53 interacted with mouse UBF in vitro, as revealed by Far‐Western blotting and GST pull down assays. These results, together with the accumulation of PAF53 in the nucleolus of growing cells, suggest that PAF53 is involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBF for the active rRNA synthesis.

Our cell-based assay is useful for anti-cN1A autoantibodies detection. Patients with anti-cN1A autoantibodies demonstrated unique clinicopathological features. In vitro and in vivo passive immunization model results suggest that anti-cN1A autoantibodies may affect protein degradation in myofibers. Ann Neurol 2017;81:512-525.

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Muscle satellite cells are essential for muscle regeneration. However, efficient regeneration does not occur without muscle-resident mesenchymal progenitor cells. We show here that bone marrow-derived mesenchymal stromal cells (Bm-MSCs) also facilitate muscle regeneration in Duchenne muscular dystrophy (DMD) model mice. Bm-MSCs transplanted into peritoneal cavities of DMD model mice with severe muscle degeneration strongly suppressed dystrophic pathology and improved death-related symptoms, which resulted in dramatic lifespan extension. Isolated single myofibers from Bm-MSC-transplanted mice manifested considerably less myofiber splitting compared with myofibers from non-transplanted mice, which indicated that transplantation significantly ameliorated abnormal regeneration. With regard to the number of satellite cells, several cells remained on myofibers from Bm-MSC-transplanted model mice, but satellite cells rarely occurred on myofibers from non-transplanted mice. Also, CXCL12 was crucial for muscle regeneration. CXCL12 facilitated muscle regeneration and paired box protein–7 (PAX7) expression after cardiotoxin-related muscle injury in vivo. The majority of primary muscle satellite cells sorted by integrin-α7 and CD34 expressed CXCR4, a receptor specific for CXCL12. CXCL12 strongly suppressed p-STAT3 expression in these sorted cells in vitro. CXCL12 may therefore influence muscle regeneration through STAT3 signaling in satellite cells. Targeting these proteins in or on muscle satellite cells may improve many degenerative muscle diseases.

Background and purposeOxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients.MethodsWe retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016.ResultsThe differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients.ConclusionOur retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS.