1,018 research outputs found

    PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.

    Get PDF
    BackgroundMaintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.MethodsWe developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC.ResultsThe level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre.ConclusionsPR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model

    Advanced ODE Based Head Modelling for Chinese Marionette Art Preservation

    Get PDF
    Puppetry has been a popular art form for many centuries in different cultures, which becomes a valuable and fascinating heritage assert. Traditional Chinese marionette art with over 2,000 years history is one of the most representative forms offering a mixture of stage performance of singing, dancing, music, poem, opera, story narrative and action. Apart from a set of string rules which controls the dynamics, head carving skill is another important pillar in this art form. This paper addresses the heritage preservation of the marionette head carving by digitalizing the head models with a novel modelling technique using ordinary differential equations (ODEs). The technique has been specially tailored to suit the modelling complexity and the need of accurate description of shapes. It offers smoothly sewing ODE swept patches to represent the distinct features of a marionette head with sharp variance of local geometry. Such features otherwise are difficult to model and capture accurately, which may require a great effort and tedious hand-crafting of an experienced modeller, when using other representation forms like polygons

    Two-photon double ionization of helium: Evolution of the joint angular distribution with photon energy and two-electron energy sharing

    Get PDF
    Ab initio calculations of two-photon double ionization of helium with photon energies varying from the nonsequential regime to well above the double-ionization threshold are presented. A systematic study of the joint angular distributions of the two ionized electrons at different energy sharing shows that the role of electron correlations is imprinted in the joint angular distribution. In particular, a rather general pattern is identified in the nonsequential regime that is independent of photon energy, pulse length, and energy sharing between the two electrons. Interestingly, the same distribution pattern is found for the equal-energy-sharing case, even when the photon energy is well above the double-ionization threshold. In the case of an extremely uneven energy sharing, the distribution pattern changes drastically as the photon energy is increased. In particular, when the photon energy is greater than the second-ionization threshold, the dominant emission mode of the two electrons switches gradually from “back to back” to “side by side.” Finally, the joint angular distribution is found to provide clear evidence of the role of electron correlations in the initial state

    Inhibition of cyclin-dependent kinase 7 down-regulates yes-associated protein expression in mesothelioma cells.

    Get PDF
    Cyclin-dependent kinase 7 (CDK7) is a protein kinase that plays a major role in transcription initiation. Yes-associated protein (YAP) is a main effector of the Hippo/YAP signalling pathway. Here, we investigated the role of CDK7 on YAP regulation in human malignant pleural mesothelioma (MPM). We found that in microarray samples of human MPM tissue, immunohistochemistry staining showed correlation between the expression level of CDK7 and YAP (n = 70, r = .513). In MPM cells, CDK7 expression level was significantly correlated with GTIIC reporter activity (r = .886, P = .019). Inhibition of CDK7 by siRNA decreased the YAP protein level and the GTIIC reporter activity in the MPM cell lines 211H, H290 and H2052. Degradation of the YAP protein was accelerated after CDK7 knockdown in 211H, H290 and H2052 cells. Inhibition of CDK7 reduced tumour cell migration and invasion, as well as tumorsphere formation ability. Restoration of the CDK7 gene rescued the YAP protein level and GTIIC reporter activity after siRNA knockdown in 211H and H2052 cells. Finally, we performed a co-immunoprecipitation analysis using an anti-YAP antibody and captured the CDK7 protein in 211H cells. Our results suggest that CDK7 inhibition reduces the YAP protein level by promoting its degradation and suppresses the migration and invasion of MPM cells. Cyclin-dependent kinase 7 may be a promising therapeutic target for MPM

    A Google Earth-based surveillance system for schistosomiasis japonica implemented in the lower reaches of the Yangtze River, China

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Due to the success of the national schistosomiasis control programme in China, transmission has been sufficiently reduced in many areas to severely limit identification of areas at risk by conventional snail surveys only. In this study, we imported Google Earth technology and a Global Positioning System (GPS) into the monitoring system for schistosomiasis surveillance of the banks of the Yangtze River in Jiangsu Province, China.</p> <p>Methods</p> <p>A total of 45 sites were selected and the risk was assessed monthly by water exposure of sentinel mice at these sites from May to September in 2009 and 2010. The results were assembled and broadcast via the Google Earth platform.</p> <p>Results</p> <p>The intensity of schistosomiasis transmission showed peaks of risk in June and September of 2009, while there was only one small peak in June in 2010 as the number of detected positive transmission sites dropped dramatically that year thanks to improved mollusciciding. River ports were found to be areas of particular risk, but ferry terminals and other centres of river-related activities were also problematic.</p> <p>Conclusions</p> <p>The results confirm that the surveillance system can be rapidly updated and easily maintained, which proves the Google Earth approach to be a user-friendly, inexpensive warning system for schistosomiasis risk.</p
    corecore