No abstract

The mitotic spindle is composed of dynamic microtubules and associated proteins that together direct chromosome movement during mitosis. The spindle plays a vital role in accurate chromosome segregation fidelity and is a therapeutic target in cancer. Nevertheless, the molecular mechanisms by which many spindle-associated proteins function remains unknown. The cleolar andpindle-ssociated rotein NUSAP1 is a microtubule-binding protein implicated in spindle stability and chromosome segregation. We show here that NUSAP1 localizes to dynamic spindle microtubules in a unique chromosome-centric pattern, in the vicinity of overlapping microtubules, during metaphase and anaphase of mitosis. Mass spectrometry-based analysis of endogenous NUSAP1 interacting proteins uncovered a cell cycle-regulated interaction between the RanBP2-RanGAP1-UBC9 SUMO E3 ligase complex and NUSAP1. Like NUSAP1 depletion, RanBP2 depletion impaired the response of cells to the microtubule poison Taxol. NUSAP1 contains a conserved SAP domain (SAF-A/B, Acinus, and PIAS). SAP domains are common among many other SUMO E3s, and are implicated in substrate recognition and ligase activity. We speculate that NUSAP1 contributes to accurate chromosome segregation by acting as a co-factor for RanBP2-RanGAP1-UBC9 during cell division.

Black hole (BH) spin can play an important role in galaxy evolution by controlling the amount of energy and momentum ejected from near the BH into the surroundings. We focus on the magnetically-arrested disk (MAD) state in the sub-and super-Eddington regimes, when the accretion disk is radiatively-inefficient and geometrically-thick, and the system launches strong BH-powered jets. Using a suite of 3D general relativistic magnetohydrodynamic (GRMHD) simulations, we find that for any initial spin, a MAD rapidly spins down the BH to the equilibrium spin of 0 < a eq 0.1, very low compared to a eq = 1 for the standard thin luminous (Novikov-Thorne) disks. This implies that rapidly accreting (super-Eddington) BHs fed by MADs tend to lose most of their rotational energy to magnetized relativistic outflows. In a MAD, a BH only needs to accrete 10% of its own mass to spin down from a = 1 to a = 0.2. We construct a semi-analytic model of BH spin evolution in MADs by taking into account the torques on the BH due to both the hydrodynamic disk and electromagnetic jet components, and find that the low value of a eq is due to both the jets slowing down the BH rotation and the disk losing a large fraction of its angular momentum to outflows. Our results have crucial implications on how BH spins evolve in active galaxies and other systems such as collapsars, where BH spin-down timescale can be short enough to significantly affect the evolution of BH-powered jets.

Politics often explains where development assistance has been effective and where it has not. Yet, until the 2000s there has been little focus by development agencies on political issues. This has recently begun to change with political‐economy analysis (PEA) now being more systematically used by development agencies to understand the real world. Nigeria and Bangladesh are two positive examples. Much remains to be done in these countries and more widely, to ensure stronger uptake of PEA. On the supply side this includes getting the ‘product’ right, and better communicating the message. On the demand side, there is a need to take more account of the incentives facing development agencies and to gather more systematic evidence on the operational impact of PEA to date.