1,791 research outputs found

    Bub2 regulation of cytokinesis and septation in budding yeast

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    <p>Abstract</p> <p>Background</p> <p>The mitotic exit network (MEN) is required for events at the end of mitosis such as degradation of mitotic cyclins and cytokinesis. Bub2 and its binding partner Bfa1 act as a GTPase activating protein (GAP) to negatively regulate the MEN GTPase Tem1. The Bub2/Bfa1 checkpoint pathway is required to delay the cell cycle in response to mispositioned spindles. In addition to its role in mitotic exit, Tem1 is required for actomyosin ring contraction.</p> <p>Results</p> <p>To test the hypothesis that the Bub2 pathway prevents premature actin ring assembly, we compared the timing of actin ring formation in wild type, <it>bub2Δ</it>, <it>mad2Δ</it>, and <it>bub2Δmad2Δ </it>cells both with and without microtubules. There was no difference in the timing of actin ring formation between wild type and mutant cells in a synchronized cell cycle. In the presence of nocodazole, both <it>bub2Δ </it>and <it>mad2Δ </it>cells formed rings after a delay of the same duration. Double mutant <it>bub2Δmad2Δ </it>and <it>bfa1Δmad2Δ </it>cells formed rings at the same time with and without nocodazole. To determine if Bub2 has an effect on actomyosin ring contraction through its regulation of Tem1, we used live cell imaging of Myo1-GFP in a <it>bub2Δ </it>strain. We found a significant decrease in the total time of contraction and an increase in rate of contraction compared to wild type cells. We also examined myosin contraction using Myo1-GFP in cells overexpressing an epitope tagged Bub2. Surprisingly, overexpression of Bub2 also led to a significant increase in the rate of contraction, as well as morphological defects. The chained cell phenotype caused by Bub2 overexpression could be rescued by co-overexpression of Tem1, and was not rescued by deletion of <it>BFA1</it>.</p> <p>Conclusion</p> <p>Our data indicate that the Bub2 checkpoint pathway does not have a specific role in delaying actin ring formation. The observed increase in the rate of myosin contraction in the <it>bub2Δ </it>strain provides evidence that the MEN regulates actomyosin ring contraction. Our data suggest that the overexpression of the Bub2 fusion protein acts as a dominant negative, leading to septation defects by a mechanism that is Tem1-dependent.</p

    Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged \u3c5 Years in the PERCH Study.

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    Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study

    Parenting while living with advanced cancer: A qualitative study

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    Patients with advanced cancer who have dependent children are an important population with a life-limiting illness and high levels of psychological distress. Few studies have addressed the experience of being a parent with advanced cancer and their potential palliative needs

    The First Quiescent Galaxies in TNG300

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    We identify the first quiescent galaxies in TNG300, the largest volume of the IllustrisTNG cosmological simulation suite, and explore their quenching processes and time evolution to z=0. We find that the first quiescent galaxies with stellar masses M_* > 3 x 10^{10} M_sun and specific star formation rates sSFR < 10^{-11} yr^{-1} emerge at z~4.2 in TNG300. Suppression of star formation in these galaxies begins with a thermal mode of AGN feedback at z~6, and a kinetic feedback mode acts in each galaxy by z~4.7 to complete the quenching process, which occurs on a time-scale of ~0.35 Gyr. Surprisingly, we find that the majority of these galaxies are not the main progenitors of their z=0 descendants; instead, four of the five galaxies fall into more massive galaxies in subsequent mergers at a range of redshifts 2.5 < z < 0.2. By z=0, these descendants are the centres of galaxy clusters with average stellar masses of 8 x 10^{11} M_sun. We make predictions for the first quenched galaxies to be located by the James Webb Space Telescope (JWST).Comment: 6 pages, 4 figure

    Indirect Detection of a Light Higgsino Motivated by Collider Data

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    Kane and Wells recently argued that collider data point to a Higgsino-like lightest supersymmetric partner which would explain the dark matter in our Galactic halo. They discuss direct detection of such dark-matter particles in laboratory detectors. Here, we argue that such a particle, if it is indeed the dark matter, might alternatively be accessible in experiments which search for energetic neutrinos from dark-matter annihilation in the Sun. We provide accurate analytic estimates for the rates which take into account all relevant physical effects. Currently, the predicted signal falls roughly one to three orders of magnitude below experimental bounds, depending on the mass and coupling of the particle; however, detectors such as MACRO, super-Kamiokande, and AMANDA will continue to take data and should be able to rule out or confirm an interesting portion of the possible mass range for such a dark-matter particle within the next five years.Comment: 10 pages, RevTe
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