| 1. |
- Bisteau, Xavier, et al.
(författare)
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The Greatwall kinase safeguards the genome integrity by affecting the kinome activity in mitosis
- 2020
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594.
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Tidskriftsartikel (refereegranskat)abstract
- Progression through mitosis is balanced by the timely regulation of phosphorylation and dephosphorylation events ensuring the correct segregation of chromosomes before cytokinesis. This balance is regulated by the opposing actions of CDK1 and PP2A, as well as the Greatwall kinase/MASTL. MASTL is commonly overexpressed in cancer, which makes it a potential therapeutic anticancer target. Loss of Mastl induces multiple chromosomal errors that lead to the accumulation of micronuclei and multilobulated cells in mitosis. Our analyses revealed that loss of Mastl leads to chromosome breaks and abnormalities impairing correct segregation. Phospho-proteomic data for Mastl knockout cells revealed alterations in proteins implicated in multiple processes during mitosis including double-strand DNA damage repair. In silico prediction of the kinases with affected activity unveiled NEK2 to be regulated in the absence of Mastl. We uncovered that, RAD51AP1, involved in regulation of homologous recombination, is phosphorylated by NEK2 and CDK1 but also efficiently dephosphorylated by PP2A/B55. Our results suggest that MastlKO disturbs the equilibrium of the mitotic phosphoproteome that leads to the disruption of DNA damage repair and triggers an accumulation of chromosome breaks even in noncancerous cells.
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| 2. |
- Neumann, Patrick, et al.
(författare)
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Trunk posture: reliability, accuracy, and risk estimates for low back pain from a video based assessment method
- 2001
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Ingår i: International Journal of Industrial Ergonomics. - 0169-8141. ; 28, s. 355-365
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Tidskriftsartikel (refereegranskat)abstract
- It has been recently reported that both dynamic movement characteristics, as well as the duration of postures adopted during work, are important in the development of low back pain (LBP). This paper presents a video-based posture assessment method capable of measuring trunk angles and angular velocities in industrial workplaces. The interobserver reliability, system accuracy, and the relationship of the measured exposures to the reporting of low back pain are reported. The video analysis workstation consisted of a desktop computer equipped with digital video capture and playback technology, a VCR, and a computer game type joystick. The operator could then use a joystick to track trunk flexion and lateral bending during computer-controlled video playback. The joystick buttons were used for binary input of twisting. The inter-observer reliability for peak flexion and percentage of time spent in posture category variables were excellent (ICC>0.8). Lower reliability levels were observed for peak and average velocity and movement related variables. The video analysis system time series data showed very high correlation to the criterion optoelectronic imaging system (r ¼ 0:92). Root mean square errors averaged 5.81 for the amplitude probability distribution function data. Trunk flexion variables including peak level, peak velocity, average velocity indicators, and percent time in flexion category indicators all showed significant differences between cases and controls in the epidemiological study. A model consisting of the measures peak trunk flexion, percent time in lateral bend and average lateral bending velocity emerged after multivariable analysis for relationship to low back pain.
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