ORCID Profile
0000-0001-9418-6739
Current Organisation
Utrecht University
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Publisher: eLife Sciences Publications, Ltd
Date: 11-11-2020
DOI: 10.7554/ELIFE.61302
Abstract: Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1038/S41467-021-23647-2
Abstract: Single-Molecule Localization Microscopy (SMLM) provides the ability to determine molecular organizations in cells at nanoscale resolution, but in complex biological tissues, where s le-induced aberrations h er detection and localization, its application remains a challenge. Various adaptive optics approaches have been proposed to overcome these issues, but the exact performance of these methods has not been consistently established. Here we systematically compare the performance of existing methods using both simulations and experiments with standardized s les and find that they often provide limited correction or even introduce additional errors. Careful analysis of the reasons that underlie this limited success enabled us to develop an improved method, termed REALM (Robust and Effective Adaptive Optics in Localization Microscopy), which corrects aberrations of up to 1 rad RMS using 297 frames of blinking molecules to improve single-molecule localization. After its quantitative validation, we demonstrate that REALM enables to resolve the periodic organization of cytoskeletal spectrin of the axon initial segment even at 50 μm depth in brain tissue.
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2020
DOI: 10.1101/2020.06.12.147884
Abstract: Performing Single-Molecule Localization Microscopy (SMLM) in complex biological tissues, where s le-induced aberrations h er detection and localization, has remained a challenge. Here we establish REALM (Robust and Effective Adaptive Optics in Localization Microscopy), which corrects aberrations of ≤1 rad RMS using 297 frames of blinking molecules to improve single-molecule localization. We demonstrate this method by resolving the periodic cytoskeleton of the axon initial segment at 50 μm depth in brain tissue.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2019
DOI: 10.1007/S12029-019-00343-5
Abstract: Colon cancer is predominantly a disease of older adults. Studies determining the influence of age on outcomes of colon cancer have conflicting results. We aim to determine the long-term outcomes and utilisation of adjuvant chemotherapy of older adults compared with younger adults who had had a resection of a primary colon cancer. Consecutive patients who had resection of a primary colon cancer between January 1, 2000 and December 31, 2010 were identified from a prospective database and stratified into three age groups: ≤ 69 years, 70 to 79 years, and ≥ 80 years. Age-related differences in patients, cancer, and treatment characteristics were determined by chi-square tests. Five-year overall survival and cancer-specific survival were determined by Kaplan-Meier method and by multivariable Cox regression analysis to adjust for potential confounding factors. Of 1135 included patients, 469 (41%) patients were aged ≤ 69 years, 382 (34%) were 70-79 years, and 284 (25%) were ≥ 80 years. Increasing age group predicted more comorbidity (p < 0.001), cardiac comorbidity (p < 0.001), right-sided cancers (p < 0.001), and less adjuvant chemotherapy (stage III only p < 0.001). Increasing age group was associated with worse overall survival by stage (p < 0.001) but not cancer-specific survival by stage (p = 0.83). Adjuvant chemotherapy in patients with stage III colon cancer independently predicted improved overall survival (p < 0.001) and cancer-specific survival (p = 0.01). Compared with younger adults, older adults with colon cancer had worse survival outcomes and received less adjuvant chemotherapy.
Publisher: Optica Publishing Group
Date: 10-05-2022
DOI: 10.1364/BOE.451634
Publisher: eLife Sciences Publications, Ltd
Date: 30-10-2020
Publisher: Springer Science and Business Media LLC
Date: 23-06-2023
No related grants have been discovered for Lukas Kapitein.