Rad51-dependent aberrant chromosome structures at telomeres and ribosomal DNA activate the spindle assembly checkpoint.

The spindle assembly checkpoint (SAC) monitors defects in kinetochore-microtubule attachment or lack of tension at kinetochores and arrests cells at prometaphase. In fission yeast, the double mutant between pot1Δ and the helicase-dead point mutant of the RecQ helicase Rqh1 gene (rqh1-hd) accumulates Rad51-dependent recombination intermediates at telomeres and enters mitosis with those intermediates. Here, we found that SAC-dependent prometaphase arrest occurred more frequently in pot1Δ rqh1-hd double mutants than in rqh1-hd single mutants. SAC-dependent prometaphase arrest also occurred more frequently in rqh1-hd single mutants after cells were released from DNA replication block compared to the rqh1-hd single mutant in the absence of exogenous insult to the DNA. In both cases, Mad2 foci persisted longer than usual at kinetochores, suggesting a defect in kinetochore-microtubule attachment. In pot1Δ rqh1-hd double mutants and rqh1-hd single mutants released from DNA replication block, SAC-dependent prometaphase arrest was suppressed by the removal of the recombination or replication intermediates. Our results indicate that the accumulation of recombination or replication intermediates induces SAC-dependent prometaphase arrest, possibly by affecting kinetochore-microtubule attachment.

Usefulness of milnacipran in treating phantom limb pain.

BACKGROUND: Amputation of an extremity often results in the sensation of a "phantom limb" where the patient feels that the limb that has been amputated is still present. This is frequently accompanied by "phantom limb pain". We report here the use of milnacipran, a serotonin and norepinephrine reuptake inhibitor, to treat phantom limb pain after amputation of injured or diseased limbs in three patients. METHODS AND RESULTS: The severity of phantom pain before and during treatment was quantified using a visual analog scale. In one case, phantom limb pain responded partially to treatment with high doses of paroxetine, and then replacement with milnacipran further improved the pain relief and long-term full pain relief was achieved. In the two other cases, milnacipran was used as first-line treatment and phantom limb pain responded rapidly. CONCLUSION: These results suggest that milnacipran administration may be useful in phantom limb pain, possibly as a first-line treatment.

Fission yeast Pot1 and RecQ helicase are required for efficient chromosome segregation.

Pot1 is a single-stranded telomere-binding protein that is conserved from fission yeast to mammals. Deletion of Schizosaccharomyces pombe pot1(+) causes immediate telomere loss. S. pombe Rqh1 is a homolog of the human RecQ helicase WRN, which plays essential roles in the maintenance of genomic stability. Here, we demonstrate that a pot1Δ rqh1-hd (helicase-dead) double mutant maintains telomeres that are dependent on Rad51-mediated homologous recombination. Interestingly, the pot1Δ rqh1-hd double mutant displays a "cut" (cell untimely torn) phenotype and is sensitive to the antimicrotubule drug thiabendazole (TBZ). Moreover, the chromosome ends of the double mutant do not enter the pulsed-field electrophoresis gel. These results suggest that the entangled chromosome ends in the pot1Δ rqh1-hd double mutant inhibit chromosome segregation, signifying that Pot1 and Rqh1 are required for efficient chromosome segregation. We also found that POT1 knockdown, WRN-deficient human cells are sensitive to the antimicrotubule drug vinblastine, implying that some of the functions of S. pombe Pot1 and Rqh1 may be conserved in their respective human counterparts POT1 and WRN.

Paternal overprotection in obsessive-compulsive disorder and depression with obsessive traits.

Previous studies have indicated that a parental rearing style showing a low level of care on the parental bonding instrument (PBI) is a risk factor for depression, and that there is a relationship between the overprotective rearing style on the PBI and obsessive-compulsive disorder (OCD). However, there is no study on the parental rearing attitudes in depressive patients divided into two groups based on their obsessive traits. In this study, we evaluated the parental rearing attitudes and examined the differences among four groups: depressive patients with severe obsessive traits, depressive patients with mild obsessive traits, OCD patients, and healthy volunteers. We divided the depressive patients into severe and mild groups based on their obsessive traits on the Mausdley Obsessional-Compulsive Inventory (MOCI). We compared PBI scores among four groups of 50 subjects matched for age and sex: depressive patients with severe obsessive traits, depressive patients with mild obsessive traits, OCD patients, and healthy volunteers. The paternal protection scores in the depressive patients with severely obsessive traits and the OCD patients were significantly higher than those in the depressive patients with mildly obsessive traits and healthy volunteers. This study indicated that the depressive patients with severe obsessive traits and the OCD patients have similar paternal controlling and interfering rearing attitudes. We conclude that the paternal controlling and interfering rearing attitudes are linked to the development of OCD and depression with obsessive traits, and are not linked to the development of depression itself.