947 research outputs found

    Genome-wide analysis demonstrates conserved localization of messenger RNAs to mitotic microtubules

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    RNA localization is of critical importance in many fundamental cell biological and developmental processes by regulating the spatial control of gene expression. To investigate how spindle-localized RNAs might influence mitosis, we comprehensively surveyed all messenger RNAs (mRNAs) that bound to microtubules during metaphase in both Xenopus laevis egg extracts and mitotic human cell extracts. We identify conserved classes of mRNAs that are enriched on microtubules in both human and X. laevis. Active mitotic translation occurs on X. laevis meiotic spindles, and a subset of microtubule-bound mRNAs (MT-mRNAs) associate with polyribosomes. Although many MT-mRNAs associate with polyribosomes, we find that active translation is not required for mRNA localization to mitotic microtubules. Our results represent the first genome-wide survey of mRNAs localized to a specific cytoskeletal component and suggest that microtubule localization of specific mRNAs is likely to function in mitotic regulation and mRNA segregation during cell division

    The Effect of Expanded Antiretroviral Treatment Strategies on the HIV Epidemic among Men Who Have Sex with Men in San Francisco

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    Modeling of expanding antiretroviral treatment to all HIV infected adults already in care in San Francisco predicts reductions in new HIV infections at 5 years of 59% among men who have sex with men (MSM). Addition of annual HIV testing for MSM to universal treatment decreases new infections by 76%

    Inductive Reasoning Games as Influenza Vaccination Models: Mean Field Analysis

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    We define and analyze an inductive reasoning game of voluntary yearly vaccination in order to establish whether or not a population of individuals acting in their own self-interest would be able to prevent influenza epidemics. We find that epidemics are rarely prevented. We also find that severe epidemics may occur without the introduction of pandemic strains. We further address the situation where market incentives are introduced to help ameliorating epidemics. Surprisingly, we find that vaccinating families exacerbates epidemics. However, a public health program requesting prepayment of vaccinations may significantly ameliorate influenza epidemics.Comment: 20 pages, 7 figure

    Fast regridding of large, complex geospatial datasets

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    Fast regridding of large, comple

    RNA Stimulates Aurora B Kinase Activity during Mitosis

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    Accurate chromosome segregation is essential for cell viability. The mitotic spindle is crucial for chromosome segregation, but much remains unknown about factors that regulate spindle assembly. Recent work implicates RNA in promoting proper spindle assembly independently of mRNA translation; however, the mechanism by which RNA performs this function is currently unknown. Here, we show that RNA regulates both the localization and catalytic activity of the mitotic kinase, Aurora-B (AurB), which is present in a ribonucleoprotein (RNP) complex with many mRNAs. Interestingly, AurB kinase activity is reduced in Xenopus egg extracts treated with RNase, and its activity is stimulated in vitro by RNA binding. Spindle assembly defects following RNase-treatment are partially rescued by inhibiting MCAK, a microtubule depolymerase that is inactivated by AurB-dependent phosphorylation. These findings implicate AurB as an important RNA-dependent spindle assembly factor, and demonstrate a translation-independent role for RNA in stimulating AurB

    Drosophila CENP-A Mutations Cause a BubR1- Dependent Early Mitotic Delay without Normal Localization of Kinetochore Components

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    The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC), which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID) display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization
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