Cells arrested in mitosis by inactivation of the APC/C complex sometimes manage to exit mitosis in a process called mitotic slippage, which helps cancer cells circumvent chemotherapy drugs. Balachandran et al. show that mitotic slippage occurs as a result of targeting of cyclin B1 for degradation by the ligase CRL2ZYG11.
The theory of special relativity derives from the Lorentz transformation. The Lorentz transformation implies differential simultaneity and light speed isotropy. Experiments to probe differential simultaneity should be able to distinguish the Lorentz transformation from a kinematically-similar alternate transformation that predicts absolute simultaneity, the absolute Lorentz transformation. Here, we describe how published optical tests of light speed isotropy/anisotropy cannot distinguish between the two transformations. We show that the shared equations of the two transformations, from the perspective of the "stationary" observer, are sufficient to predict null results in optical resonator experiments and in tests of frequency changes in one-way light paths. In an influential 1910 exposition on differential simultaneity, Comstock described how a "stationary" observer would observe different clock readings for spatially-separated "moving" clocks. The difference in clock readings is an integral aspect of differential simultaneity. We derive the equation for the difference in clock readings and show that it is equivalent to the Sagnac correction that describes light speed anisotropies in satellite communications. We describe an experimental strategy that can measure the differences in spatially-separated clock times to allow a direct probe of the nature of simultaneity.
Rotational transformations describe relativistic effects in rotating frames. There are four major kinematic rotational transformations: the Langevin metric; Post transformation; Franklin transformation; and the rotational form of the absolute Lorentz transformation. The four transformations exhibit different combinations of relativistic effects and simultaneity frameworks, and generate different predictions for relativistic phenomena. Here, the predictions of the four rotational transformations are compared with recent optical data that has sufficient resolution to distinguish the transformations. We show that the rotational absolute Lorentz transformation matches diverse relativistic optical and non-optical rotational data. These include experimental observations of length contraction, directional time dilation, anisotropic one-way speed of light, isotropic two-way speed of light, and the conventional Sagnac effect. In contrast, the other three transformations do not match the full range of rotating-frame relativistic observations.
Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions.
Mitosis inhibitors, which include antimicrotubule drugs, are chemotherapy agents that induce the arrest and apoptosis of mitotic cells. Mitotic slippage, in which mitotically arrested cells exit mitosis, limits the effectiveness of mitosis inhibitors. We have discovered that the CRL2ZYG11A/B ubiquitin ligase promotes mitotic slippage. The combination of antimicrotubule drugs and a CRL2ZYG11A/B inhibitor prevents mitotic slippage to increase antimitotic efficacy.
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