Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication

Centrosome duplication is tightly controlled in coordination with DNA replication. The molecular mechanism of centrosome duplication remains unclear. Previous studies found that a fraction of human proline-directed phosphatase Cdc14B associates with centrosomes. However, Cdc14B's involvement in centrosome cycle control has never been explored. Here, we show that depletion of Cdc14B by RNA interference leads to centriole amplification in both HeLa and normal human fibroblast BJ and MRC-5 cells. Induction of Cdc14B expression through a regulatable promoter significantly attenuates centriole amplification in prolonged S phase–arrested cells and proteasome inhibitor Z-L3VS–treated cells. This inhibitory function requires centriole-associated Cdc14B catalytic activity. Together, these results suggest a potential function for Cdc14B phosphatase in maintaining the fidelity of centrosome duplication cycle

Web-based infectious disease surveillance systems and public health perspectives: a systematic review

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Emerging and re-emerging infectious diseases are a significant public health concern, and early detection and immediate response is crucial for disease control. These challenges have led to the need for new approaches and technologies to reinforce the capacity of traditional surveillance systems for detecting emerging infectious diseases. In the last few years, the availability of novel web-based data sources has contributed substantially to infectious disease surveillance. This study explores the burgeoning field of web-based infectious disease surveillance systems by examining their current status, importance, and potential challenges. Methods A systematic review framework was applied to the search, screening, and analysis of web-based infectious disease surveillance systems. We searched PubMed, Web of Science, and Embase databases to extensively review the English literature published between 2000 and 2015. Eleven surveillance systems were chosen for evaluation according to their high frequency of application. Relevant terms, including newly coined terms, development and classification of the surveillance systems, and various characteristics associated with the systems were studied. Results Based on a detailed and informative review of the 11 web-based infectious disease surveillance systems, it was evident that these systems exhibited clear strengths, as compared to traditional surveillance systems, but with some limitations yet to be overcome. The major strengths of the newly emerging surveillance systems are that they are intuitive, adaptable, low-cost, and operated in real-time, all of which are necessary features of an effective public health tool. The most apparent potential challenges of the web-based systems are those of inaccurate interpretation and prediction of health status, and privacy issues, based on an individuals internet activity. Conclusion Despite being in a nascent stage with further modification needed, web-based surveillance systems have evolved to complement traditional national surveillance systems. This review highlights ways in which the strengths of existing systems can be maintained and weaknesses alleviated to implement optimal web surveillance systems

The Dual-Specificity Phosphatase CDC14B Bundles and Stabilizes Microtubules

The Cdc14 dual-specificity phosphatases regulate key events in the eukaryotic cell cycle. However, little is known about the function of mammalian CDC14B family members. Here, we demonstrate that subcellular localization of CDC14B protein is cell cycle regulated. CDC14B can bind, bundle, and stabilize microtubules in vitro independently of its catalytic activity. Basic amino acid residues within the nucleolar targeting domain are important for both retaining CDC14B in the nucleolus and preventing microtubule bundling. Overexpression of CDC14B resulted in the formation of cytoplasmic CDC14B and microtubule bundles in interphase cells. These microtubule bundles were resistant to microtubule depolymerization reagents and enriched in acetylated α-tubulin. Expression of cytoplasmic forms of CDC14B impaired microtubule nucleation from the microtubule organization center. CDC14B is thus a novel microtubule-bundling and -stabilizing protein, whose regulated subcellular localization may help modulate spindle and microtubule dynamics in mitosis

(A) Representative confocal images of BJ and MRC-5 cells with clustered supernumerary centrioles are shown

Centrioles were labeled by anti-centrin antibody. Insets show magnified images of centrioles. Bar, 10 μm. (B) The percentage of cells with more than four centrioles was calculated from the experiments shown in A. Data shown represent the means ± SD of three independent experiments. At least 300 cells were counted in each experiment.<p><b>Copyright information:</b></p><p>Taken from "Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication"</p><p></p><p>The Journal of Cell Biology 2008;181(3):475-483.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364701.</p><p></p

(A, top) Cdc14B-GFP fusion proteins were induced by 4 μg/ml DOX in the presence of 2 mM HU for 72 h in U2OS Tet-On stable cell lines carrying different Cdc14B-GFP constructs as indicated

Centrioles were visualized by anti-centrin staining (red) and overlaid with Cdc14B-GFP (green) and DAPI (blue). Note that Cdc14B-GFP was not detectable at centrioles (arrow). Insets show magnified images of centrioles. Bar, 5 μm. (bottom) The percentage of cells with more than four centrioles was calculated from both induced (+DOX) and uninduced (−DOX) Cdc14B-GFP stable clones as indicated. Data shown represent the means ± SD of three independent experiments from two individual Cdc14B-GFP stable clones. At least 500 cells were counted in each experiment. (B, top) U2OS Tet-On cells were transfected as indicated. 16 h after transfection, cells were incubated with (+HU) or without (−HU) 2 mM HU and 4 μg/ml DOX for 72 h. Centrosomes were visualized by γ-tubulin staining (red). Representative centrosome amplification was detected in mock-transfected cells after HU treatment but not in pBI-tet-Cdc14B-GFP transfected cells where Cdc14B-GFP (green) associated with centrosomes. Insets show magnified images of centrosomes. DAPI (blue), DNA. Bar, 5 μm. (bottom) The percentage of cells with the indicated centrosome numbers was calculated from the experiments shown in the top panel. Centrosomes were counted in both mock and Cdc14B-GFP–transfected cells (Cdc14B-GFP–positive at centrosomes). All the data are shown as the means ± SD of three independent experiments. At least 500 cells were counted in each experiment. (C) Representative fluorescence-activated cell sorting profile on cell cycle distribution of DOX-inducible Cdc14B-GFP U2OS Tet-On stable clones. Cells were cultivated in the presence or absence of 4 μg/ml DOX for 72 h. Positions of cells with 2 N and 4 N DNA contents are labeled with arrowheads.<p><b>Copyright information:</b></p><p>Taken from "Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication"</p><p></p><p>The Journal of Cell Biology 2008;181(3):475-483.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364701.</p><p></p

(A) Cdc14B-GFP fusion proteins were induced by DOX for 72 h in U2OS Tet-On stable cell lines carrying different Cdc14B-GFP constructs as indicated

Centrosomes were visualized by γ-tubulin staining (red) and overlaid with Cdc14B-GFP (green) and DAPI-stained DNA (blue). Cdc14B-GFP was not detectable at interphase or mitotic centrosomes (arrows). Insets represent magnified images of centrosomes. Bar, 5 μm. (B) Histogram shows the percentage of interphase and mitotic cells with the indicated Cdc14B-GFP at centrosomes 72 h after DOX addition. The interphase data represent the means ± SD of three independent experiments and at least 500 cells were counted in each experiment. The mitotic experiment was performed in triplicates and a total of 113 Cdc14B-GFP– and 374 Cdc14B-GFP–positive cells were counted.<p><b>Copyright information:</b></p><p>Taken from "Cdc14B depletion leads to centriole amplification, and its overexpression prevents unscheduled centriole duplication"</p><p></p><p>The Journal of Cell Biology 2008;181(3):475-483.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364701.</p><p></p