The Role of Hklp2 in the Stabilization and Maintenance of Spindle Bipolarity

SummarySpindle bipolarity relies on a fine balance of forces exerted by various molecular motors [1–4]. In most animal cells, spindle bipolarity requires sustained outward forces to push the spindle poles apart, an activity that is provided by Eg5, a conserved homotetrameric plus-end-directed kinesin that crosslinks and slides antiparallel microtubules apart [5]. These pushing forces are balanced by inward minus-end-directed forces. Impairing both Eg5 and dynein restores the formation of functional bipolar spindles [4], although the mechanism at play is far from clear. The current model also fails to explain why in some systems Eg5 inhibition does not promote bipolar spindle collapse [6, 7] or why increasing Eg5 levels does not interfere with bipolar spindle assembly [8]. Moreover, the C. elegans Eg5 ortholog is not required for bipolar spindle formation [9]. We show here that the kinesin Hklp2 participates in the assembly and stabilization of the bipolar spindle. Hklp2 localizes to the mitotic microtubules in a TPX2-dependent manner and to the chromosomes through Ki67. Our data indicate that its mechanism of action is clearly distinct from and complementary to that of Eg5, providing an additional understanding of the mechanism driving the formation and maintenance of the bipolar spindle

The Usefulness of Short Physical Performance Battery Score for Predicting the Ability of Toilet Activity in Hospitalized Older Patients

Background: It has been still unclear whether the cut-off value of the short physical performance battery for predicting the ability of the toilet activity in the hospitalized older patients. The aim of this study was to reveal the relationship between the short physical performance battery and the ability of toilet activity, and also to determine the cut-off value of the short physical performance battery score for the ability of toilet activity in the hospitalized older patients. Methods: In this cross-sectional study, 71 hospitalized older patients were recruited. The short physical performance battery and the ability of toilet activity using the Barthel index (BI) were measured. The patients were split into two groups, according to the ability of toilet activity (Group 1: 10 point; Group 2: 5 point or less in BI score). A multiple logistic regression analysis was used to assess the relationship between the two groups. Moreover, the cut-off value for dividing into two groups, (Group 1 and Group 2) using the short physical performance battery score, which was calculated by a receiver operating characteristic curve. Results: The short physical performance battery score was an independent explanator for the ability of toilet activity using multiple logistic regression analysis. Besides, the cut-off value of the short physical performance battery for the ability of toilet activity was set in this study. Conclusion: The findings of this study suggest that the cut-off value of the short physical performance battery score could be a useful index to predict the ability of toilet activity in the hospitalized older patients. &nbsp

Sympathetic ophthalmia after 23-gauge transconjunctival sutureless vitrectomy

We report a case of a sympathetic ophthalmia that occurred after 23-gauge transconjunctival sutureless vitrectomy for a retinal detachment

Regulation of p53 Translation and Induction after DNA Damage by Ribosomal Protein L26 and Nucleolin

SummaryIncreases in p53 protein levels after DNA damage have largely been attributed to an increase in the half-life of p53 protein. Here we demonstrate that increased translation of p53 mRNA is also a critical step in the induction of p53 protein in irradiated cells. Ribosomal protein L26 (RPL26) and nucleolin were found to bind to the 5′ untranslated region (UTR) of p53 mRNA and to control p53 translation and induction after DNA damage. RPL26 preferentially binds to the 5′UTR after DNA damage, and its overexpression enhances association of p53 mRNA with heavier polysomes, increases the rate of p53 translation, induces G1 cell-cycle arrest, and augments irradiation-induced apoptosis. Opposite effects were seen when RPL26 expression was inhibited. In contrast, nucleolin overexpression suppresses p53 translation and induction after DNA damage, whereas nucleolin downregulation promotes p53 expression. These findings demonstrate the importance of increased translation of p53 in DNA-damage responses and suggest critical roles for RPL26 and nucleolin in affecting p53 induction

Cell cycle-specific phase separation regulated by protein charge blockiness

Dynamic morphological changes of intracellular organelles are often regulated by protein phosphorylation or dephosphorylation1-6. Phosphorylation modulates stereospecific interactions among structured proteins, but how it controls molecular interactions among unstructured proteins and regulates their macroscopic behaviours remains unknown. Here we determined the cell cycle-specific behaviour of Ki-67, which localizes to the nucleoli during interphase and relocates to the chromosome periphery during mitosis. Mitotic hyperphosphorylation of disordered repeat domains of Ki-67 generates alternating charge blocks in these domains and increases their propensity for liquid–liquid phase separation (LLPS). A phosphomimetic sequence and the sequences with enhanced charge blockiness underwent strong LLPS in vitro and induced chromosome periphery formation in vivo. Conversely, mitotic hyperphosphorylation of NPM1 diminished a charge block and suppressed LLPS, resulting in nucleolar dissolution. Cell cycle-specific phase separation can be modulated via phosphorylation by enhancing or reducing the charge blockiness of disordered regions, rather than by attaching phosphate groups to specific sites