55 research outputs found

    Directional cell expansion requires NIMA-related kinase 6 (NEK6)-mediated cortical microtubule destabilization;

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     Plant cortical microtubules align perpendicular to the growth axis to determine the direction of cell growth. However, it remains unclear how plant cells form well-organized cortical microtubule arrays in the absence of a centrosome. In this study, we investigated the functions of Arabidopsis NIMA-related kinase 6 (NEK6), which regulates microtubule organization during anisotropic cell expansion. Quantitative analysis of hypocotyl cell growth in the nek6-1 mutant demonstrated that NEK6 suppresses ectopic outgrowth and promotes cell elongation in different regions of the hypocotyl. Loss of NEK6 function led to excessive microtubule waving and distortion, implying that NEK6 suppresses the aberrant cortical microtubules. Live cell imaging showed that NEK6 localizes to the microtubule lattice and to the shrinking plus and minus ends of microtubules. In agreement with this observation, the induced overexpression of NEK6 reduced and disorganized cortical microtubules and suppressed cell elongation. Furthermore, we identified five phosphorylation sites in β-tubulin that serve as substrates for NEK6 in vitro. Alanine substitution of the phosphorylation site Thr166 promoted incorporation of mutant β-tubulin into microtubules. Taken together, these results suggest that NEK6 promotes directional cell growth through phosphorylation of β-tubulin and the resulting destabilization of cortical microtubules

    Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

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    To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics

    Evaluation of Fiber/Matrix Interfacial Strength of Neutron Irradiated SiC/SiC Composites Using Hysteresis Loop Analysis of Tensile Test

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    Advanced SiC/SiC composites composed of highly-crystalline and near-stoichiometric SiC fibers, SiC matrix by CVI method, and PyC interphase were irradiated up to 1:0 Â 10 25 n/m 2 (E > 0:1 MeV, 1dpa)at1273K.Unload/reloadcyclictensiletestandhysteresisloopanalysiswerecarriedoutinordertoidentifyneutronirradiationeffectsoninterfacialpropertiesofadvancedSiC/SiC.Thecompositesexhibitedgoodirradiationresistanceinultimatetensilestrength(1 dpa) at 1273 K. Unload/reload cyclic tensile test and hysteresis loop analysis were carried out in order to identify neutron irradiation effects on interfacial properties of advanced SiC/SiC. The composites exhibited good irradiation resistance in ultimate tensile strength (10% increase), but there were slight reduction of elastic modulus and proportional limit stress (PLS) ($10%). Wider hysteresis loops and lower gradient of the curves beyond PLS from the strain-stress curves, and longer pullouts of fiber from the SEM observation were observed, which imply weaker F/M interactions after neutron irradiation. From the hysteresis loop analysis, degradation of interfacial sliding stress and negative increment of misfit stress after neutron irradiation were obtained
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