10 research outputs found

    p31 comet acts to ensure timely spindle checkpoint silencing subsequent to kinetochore attachment

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    The spindle assembly checkpoint links the onset of anaphase to completion of chromosome-microtubule attachment and is mediated by the binding of Mad and Bub proteins to kinetochores of unattached or maloriented chromosomes. Mad2 and BubR1 traffic between kinetochores and the cytosol, thereby transmitting a "wait anaphase" signal to the anaphase-promoting complex. It is generally assumed that this signal dissipates automatically upon kinetochore-microtubule binding, but it has been shown that under conditions of nocodazole-induced arrest p31comet, a Mad2-binding protein, is required for mitotic progression. In this article we investigate the localization and function of p31 comet during normal, unperturbed mitosis in human and marsupial cells. We find that, like Mad2, p31 comet traffics on and off kinetochores and is also present in the cytosol. Cells depleted of p31 comet arrest in metaphase with mature bipolar kinetochore-microtubule attachments, a satisfied checkpoint, and high cyclin B levels. Thus p31 comet is required for timely mitotic exit. We propose that p31 comet is an essential component of the machinery that silences the checkpoint during each cell cycle

    A multi-center study of COVID-19 patient prognosis using deep learning-based CT image analysis and electronic health records

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    Purpose: As of August 30th, there were in total 25.1 million confirmed cases and 845 thousand deaths caused by coronavirus disease of 2019 (COVID-19) worldwide. With overwhelming demands on medical resources, patient stratification based on their risks is essential. In this multi-center study, we built prognosis models to predict severity outcomes, combining patients� electronic health records (EHR), which included vital signs and laboratory data, with deep learning- and CT-based severity prediction. Method: We first developed a CT segmentation network using datasets from multiple institutions worldwide. Two biomarkers were extracted from the CT images: total opacity ratio (TOR) and consolidation ratio (CR). After obtaining TOR and CR, further prognosis analysis was conducted on datasets from INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3. For each data cohort, generalized linear model (GLM) was applied for prognosis prediction. Results: For the deep learning model, the correlation coefficient of the network prediction and manual segmentation was 0.755, 0.919, and 0.824 for the three cohorts, respectively. The AUC (95 CI) of the final prognosis models was 0.85(0.77,0.92), 0.93(0.87,0.98), and 0.86(0.75,0.94) for INSTITUTE-1, INSTITUTE-2 and INSTITUTE-3 cohorts, respectively. Either TOR or CR exist in all three final prognosis models. Age, white blood cell (WBC), and platelet (PLT) were chosen predictors in two cohorts. Oxygen saturation (SpO2) was a chosen predictor in one cohort. Conclusion: The developed deep learning method can segment lung infection regions. Prognosis results indicated that age, SpO2, CT biomarkers, PLT, and WBC were the most important prognostic predictors of COVID-19 in our prognosis model. © 202

    Red Devonian trilobites with green eyes from Morocco and the silicification of the trilobite exoskeleton

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    Latest Emsian (Early Devonian) sediments at the famous mud−mound− and trilobite−locality Hamar Laghdad (Tafilalt, Morocco) yielded some red−coloured remains of phacopid trilobites. Closer examination revealed that the eyes of these phacopids are often greenish in colour. EDX−analyses showed that the lenses retained their original calcitic composition, possibly greenish due to Fe−impurities, while most of the exoskeleton was silicified. The silicified parts contain elevated concentrations of iron which causes the red colour. This phenomenon is explained by the porosity of the exoskeleton in contrast to the homogeneous and massive construction of the lenses and their Mg−content. These incompletely silicified trilobites enabled a reconstruction of the silicification process in trilobites. Their diagenetic alteration probably occurred as a result of events associated with the Cretaceous transgression

    Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    [[sponsorship]]生物化學研究所[[note]]已出版;[SCI];有審查制度;具代表性[[note]]http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Drexel&SrcApp=hagerty_opac&KeyRecord=1554-8627&DestApp=JCR&RQ=IF_CAT_BOXPLO

    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    The clonal origin and clonal evolution of epithelial tumours

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    While the origin of tumours, whether from one cell or many, has been a source of fascination for experimental oncologists for some time, in recent years there has been a veritable explosion of information about the clonal architecture of tumours and their antecedents, stimulated, in the main, by the ready accessibility of new molecular techniques. While most of these new results have apparently confirmed the monoclonal origin of human epithelial (and other) tumours, there are a significant number of studies in which this conclusion just cannot be made. Moreover, analysis of many articles show that the potential impact of such considerations as patch size and clonal evolution on determinations of clonality have largely been ignored, with the result that a number of these studies are confounded. However, the clonal architecture of preneoplastic lesions provide some interesting insights — many lesions which might have been hitherto regarded as hyperplasias are apparently clonal in derivation. If this is indeed true, it calls into some question our hopeful corollary that a monoclonal origin presages a neoplastic habitus. Finally, it is clear, for many reasons, that methods of analysis which involve the disaggregation of tissues, albeit microdissected, are far from ideal and we should be putting more effort into techniques where the clonal architecture of normal tissues, preneoplastic and preinvasive lesions and their derivative tumours can be directly visualized in situ
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