| 1. |
- Helfricht, A, et al.
(författare)
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Loss of ZBTB24 impairs nonhomologous end-joining and class-switch recombination in patients with ICF syndrome
- 2020
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:11
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Tidskriftsartikel (refereegranskat)abstract
- The autosomal recessive immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite the identification of the underlying gene defects, it is unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates its auto-poly(ADP-ribosyl)ation. The zinc-finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, through its association with poly(ADP-ribose) chains, ZBTB24 protects them from degradation by poly(ADP-ribose) glycohydrolase (PARG). This facilitates the poly(ADP-ribose)-dependent assembly of the LIG4/XRCC4 complex at DNA breaks, thereby promoting error-free NHEJ. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF2 syndrome.
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| 2. |
- Lind, C. M., et al.
(författare)
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Effectiveness and usability of real-time vibrotactile feedback training to reduce postural exposure in real manual sorting work
- 2023
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 66:2, s. 198-216
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Tidskriftsartikel (refereegranskat)abstract
- Vibrotactile feedback training may be used as a complementary strategy to reduce time in demanding postures in manual handling. This study evaluated the short- and medium-term effects of concurrent posture-correction vibrotactile feedback training on trunk inclination exposure in real manual sorting work. Fifteen warehouse workers completed the training and the follow-up sessions. Trunk inclination angles were recorded using the ambulatory Smart Workwear System. Questionnaires were used for assessing system usability, perceived physical exertion, and work ability. The results showed reduced time in trunk inclination >30°, >45°, and >60°, and reductions in the 90th, 95th, and 99th percentile trunk inclination angles, when receiving feedback and immediately after feedback withdrawal. No significant reduction was retained after one and three weeks. The wearer's comfort was scored high, and the feedback did not increase the perceived cognitive demands. No significant effects attributed to changed trunk inclination exposure were observed for perceived physical exertion or work ability. The training program has the potential of contributing to reduced trunk inclination exposure in the short term. Future studies are needed to evaluate if improvements in the feedback training can transfer the short-term results to retained median- and long-term effects. Practitioner summary: A two-day training program with concurrent posture-correction vibrotactile feedback can contribute to reduced exposure of trunk inclination in real manual sorting work in the short term. More research is needed on how to design the feedback training programs in order to be effective in the long term.
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