Spindle assembly checkpoint: the third decade

The spindle assembly checkpoint controls cell cycle progression during mitosis, synchronizing it with the attachment of chromosomes to spindle microtubules. After the discovery of the mitotic arrest deficient (MAD) and budding uninhibited by benzymidazole (BUB) genes as crucial checkpoint components in 1991, the second decade of checkpoint studies (2001–2010) witnessed crucial advances in the elucidation of the mechanism through which the checkpoint effector, the mitotic checkpoint complex, targets the anaphase-promoting complex (APC/C) to prevent progression into anaphase. Concomitantly, the discovery that the Ndc80 complex and other components of the microtubule-binding interface of kinetochores are essential for the checkpoint response finally asserted that kinetochores are crucial for the checkpoint response. Nevertheless, the relationship between kinetochores and checkpoint control remains poorly understood. Crucial advances in this area in the third decade of checkpoint studies (2011–2020) are likely to be brought about by the characterization of the mechanism of kinetochore recruitment, activation and inactivation of checkpoint proteins, which remains elusive for the majority of checkpoint components. Here, we take a molecular view on the main challenges hampering this task

Rotating Rayleigh-Taylor turbulence

International audienceThe turbulent Rayleigh–Taylor system in a rotating reference frame is investigated by direct numerical simulations within the Oberbeck-Boussinesq approximation. On the basis of theoretical arguments, supported by our simulations, we show that the Rossby number decreases in time, and therefore the Coriolis force becomes more important as the system evolves and produces many effects on Rayleigh–Taylor turbulence. We find that rotation reduces the intensity of turbulent velocity fluctuations and therefore the growth rate of the temperature mixing layer. Moreover, in presence of rotation the conversion of potential energy into turbulent kinetic energy is found to be less effective and the efficiency of the heat transfer is reduced. Finally, during the evolution of the mixing layer we observe the development of a cyclone-anticyclone asymmetry

The pseudo GTPase CENP-M drives human kinetochore assembly

Basilico, Federica et al.Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore–centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching. We show that CENP-M is crucially required for the assembly and stability of a tetramer also comprising CENP-I, CENP-H, and CENP-K, the HIKM complex, which we extensively characterize through a combination of structural, biochemical, and cell biological approaches. A point mutant affecting the CENP-M/CENP-I interaction hampers kinetochore assembly and chromosome alignment and prevents kinetochore recruitment of the CENP-T/W complex, questioning a role of CENP-T/W as founder of an independent axis of kinetochore assembly. Our studies identify a single pathway having CENP-C as founder, and CENP-H/I/K/M and CENP-T/W as CENP-C-dependent followers.AM acknowledges funding by the European Union's 7th Framework Program ERC agreement KINCON and the Integrated Project MitoSys. FH is supported by the Bavarian Research Center of Molecular Biosystems and by a LMU excellent junior grant.Peer reviewe

On scaling and statistical geometry in passive scalar turbulence

We show that the statistics of a turbulent passive scalar at scales larger than the pumping may exhibit multiscaling due to a weaker mechanism than the presence of statistical conservation laws. We develop a general formalism to give explicit predictions for the large scale scaling exponents in the case of the Kraichnan model and discuss their geometric origin at small and large scale.Comment: 4 pages, 1 figur

Rayleigh--Taylor instability in a viscoelastic binary fluid

The effects of polymer additives on Rayleigh--Taylor (RT) instability of immiscible fluids is investigated using the Oldroyd-B viscoelastic model. Analytic results obtained exploiting the phase-field approach show that in polymer solution the growth rate of the instability speeds up with elasticity (but remains slower than in the pure solvent case). Numerical simulations of the viscoelastic binary fluid model confirm this picture

Intercomparison of Vaisala RS92 and RS41 Radiosonde Temperature Sensors under Controlled Laboratory Conditions

Radiosoundings are essential for weather and climate applications, as well as for calibration and validation of remote sensing observations. Vaisala RS92 radiosondes have been widely used on a global scale until 2016; although in the fall of 2013, Vaisala introduced the RS41 model to progressively replace the RS92. To ensure the highest quality and homogeneity of measurements following the transition from RS92 to RS41, intercomparisons of the two radiosonde models are needed. A methodology was introduced to simultaneously test and compare the two radiosonde models inside climatic chambers, in terms of noise, calibration accuracy, and bias in temperature measurements. A pair of RS41 and RS92 radiosondes has been tested at ambient pressure under very different temperature and humidity conditions, reproducing the atmospheric conditions that a radiosonde can meet at the ground before launch. The radiosondes have also been tested before and after fast (within ≈ 10 s) temperature changes of about ±20 °C, simulating a scenario similar to steep thermal changes that radiosondes can meet when passing from indoor to outdoor environment during the pre-launch phase. The results show that the temperature sensor of RS41 is less affected by noise and more accurate than that of RS92, with noise values less than 0.06 °C for RS41 and less than 0.1 °C for RS92. The deviation from the reference value, referred to as calibration error, is within ±0.1 °C for RS41 and the related uncertainty (hereafter with coverage factor k = 1) is less than 0.06 °C, while RS92 is affected by a cold bias in the calibration, which ranges from 0.1 °C up to a few tenths of a degree, with a calibration uncertainty less than 0.1 °C. The temperature bias between RS41 and RS92 is within ±0.1 °C, while its uncertainty is less than 0.1 °C. The fast and steep thermal changes that radiosondes can meet during the pre-launch phase might lead to a noise increase in temperature sensors during radiosoundings, up to 0.1 °C for RS41 and up to 0.3 °C for RS92, with a similar increase in their calibration uncertainty, as well as an increase in the uncertainty of their bias up to 0.3 °C

Rock temperature variability in high-altitude rockfall-prone areas

In a context of cryosphere degradation caused by climate warming, rock temperature is one of the main driving factors of rockfalls that occur on high-elevation mountain slopes. In order to improve the knowledge of this critical relationship, it is necessary to increase measurement capability of rock temperature and its variability in different lithological and slope/aspect conditions, and also to increase local scale studies, increasing the quality and the comparability of the data. This paper shows an example of metrological characterization of sensors used for rock temperature measurement in mountain regions, by means of the measurement uncertainty. Under such approach, data and results from temperature measurements carried out in the Bessanese high-elevation experimental site (Western European Alps) are illustrated. The procedures for the calibration and field characterization of sensors allow to measure temperature in different locations, depths and lithotypes, within 0.10 °C of overall uncertainty. This work has highlighted that metrological traceability is fundamental to asses data quality and establish comparability among different measurements; that there are strong differences between air temperature and near-surface rock temperature; and that there are significant differences of rock temperature acquired in different aspect conditions. Finally, solar radiation, slope/aspect conditions and lithotype, seem to be the main driving factors of rock temperature

A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B

By phosphorylating Thr3 of histone H3, Haspin promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis. Aurora B kinase, a CPC subunit, sustains chromosome bi-orientation and the spindle assembly checkpoint (SAC). Here, we characterize the small molecule 5-iodotubercidin (5-ITu) as a potent Haspin inhibitor. In vitro, 5-ITu potently inhibited Haspin but not Aurora B. Consistently, 5-ITu counteracted the centromeric localization of the CPC without affecting the bulk of Aurora B activity in HeLa cells. Mislocalization of Aurora B correlated with dephosphorylation of CENP-A and Hec1 and SAC override at high nocodazole concentrations. 5-ITu also impaired kinetochore recruitment of Bub1 and BubR1 kinases, and this effect was reversed by concomitant inhibition of phosphatase activity. Forcing localization of Aurora B to centromeres in 5-ITu also restored Bub1 and BubR1 localization but failed to rescue the SAC override. This result suggests that a target of 5-ITu, possibly Haspin itself, may further contribute to SAC signaling downstream of Aurora B