RESUMEN
Micronuclei resulting from improper chromosome segregation foster chromosome rearrangements.1,2 To prevent micronuclei formation in mitosis, the dynamic plus ends of bundled kinetochore microtubules (k-fibers) must establish bipolar attachment with all sister kinetochores on chromosomes,3 whereas k-fiber minus ends must be clustered at the two opposing spindle poles, which are normally connected with centrosomes.4 The establishment of chromosome biorientation via k-fiber plus ends is carefully monitored by the spindle assembly checkpoint (SAC).5 However, how k-fiber minus-end clustering near centrosomes is maintained and monitored remains poorly understood. Here, we show that degradation of NuMA by auxin-inducible degron technologies results in micronuclei formation through k-fiber minus-end detachment from spindle poles during metaphase in HCT116 colon cancer cells. Importantly, k-fiber minus-end detachment from one pole creates misaligned chromosomes that maintain chromosome biorientation and satisfy the SAC, resulting in abnormal chromosome segregation. NuMA depletion also causes minus-end clustering defects in non-transformed Rpe1 cells, but it additionally induces centrosome detachment from partially focused poles, resulting in highly disorganized anaphase. Moreover, we find that NuMA depletion causes centrosome clustering defects in tetraploid-like cells, leading to an increased frequency of multipolar divisions. Together, our data indicate that NuMA is required for faithful chromosome segregation in human mitotic cells, generally by maintaining k-fiber minus-end clustering but also by promoting spindle pole-centrosome or centrosome-centrosome connection in specific cell types or contexts. Similar to erroneous merotelic kinetochore attachments,6 detachment of k-fiber minus ends from spindle poles evades spindle checkpoint surveillance and may therefore be a source of genomic instability in dividing cells.
Asunto(s)
Huso Acromático , Polos del Huso , Humanos , Centrosoma/metabolismo , Segregación Cromosómica , Cinetocoros , Microtúbulos/metabolismo , Mitosis , Huso Acromático/metabolismo , Polos del Huso/metabolismoRESUMEN
We carried out three experiments to examine the influence of field of view and binocular viewing restrictions on absolute distance perception in real-world indoor environments. Few of the classical visual cues provide direct information for accurate absolute distance judgments to points in the environment beyond about 2 m from the viewer. Nevertheless, in previous work it has been found that visually directed walking tasks reveal accurate distance estimations in full-cue real-world environments to distances up to 20 m. In contrast, the same tasks in virtual environments produced with head-mounted displays (HMDs) show large compression of distance. Field of view and binocular viewing are common limitations in research with HMDs, and have been rarely studied under full pictorial-cue conditions in the context of distance perception in the real-world. Experiment 1 showed that the view of one's body and feet on the floor was not necessary for accurate distance perception. In experiment 2 we manipulated the horizontal and the vertical field of view along with head rotation and found that a restricted field of view did not affect the accuracy of distance estimations when head movement was allowed. Experiment 3 showed that performance with monocular viewing was equal to that with binocular viewing. These results have implications for the information needed to scale egocentric distance in the real-world and reduce the support for the hypothesis that a limited field of view or imperfections in binocular image presentation are the cause of the underestimation seen with HMDs.
Asunto(s)
Percepción de Distancia/fisiología , Enmascaramiento Perceptual/fisiología , Adulto , Señales (Psicología) , Ambiente , Femenino , Movimientos de la Cabeza/fisiología , Humanos , Masculino , Privación Sensorial/fisiología , Visión Binocular/fisiología , Visión Monocular/fisiología , Caminata/fisiologíaRESUMEN
In 4 experiments, the authors varied the extent and nature of participant movement in a virtual environment to examine the influence of action on estimates of geographical slant. Previous studies showed that people consciously overestimate hill slant but can still accurately guide an action toward the hill (D. R. Proffitt, M. Bhalla, R. Gossweiler, & J. Midgett, 1995). Related studies suggest that one's potential to act may influence perception of slant and that distinct representations may independently inform perceptual and motoric responses. The authors found that in all conditions, perceptual judgments were overestimated and motoric adjustments were more accurate. The virtual environment allowed manipulation of the effort required to walk up simulated hills. Walking with the effort appropriate to the visual slant led to increased perceptual overestimation of slant compared with active walking with the effort appropriate to level ground, while visually guided actions remained accurate.