25,301 research outputs found

    Expression of the IL-11 Gene in Metastatic Cells Is Supported by Runx2-Smad and Runx2-cJun Complexes Induced by TGFβ1.

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    In tumor cells, two factors are abnormally increased that contribute to metastatic bone disease: Runx2, a transcription factor that promotes expression of metastasis related and osteolytic genes; and IL-11, a secreted osteolytic cytokine. Here, we addressed a compelling question: Does Runx2 regulate IL-11 gene expression? We find a positive correlation between Runx2, IL-11 and TGFβ1, a driver of the vicious cycle of metastatic bone disease, in prostate cancer (PC) cell lines representing early (LNCaP) and late (PC3) stage disease. Further, like Runx2 knockdown, IL-11 knockdown significantly reduced expression of several osteolytic factors. Modulation of Runx2 expression results in corresponding changes in IL-11 expression. The IL-11 gene has Runx2, AP-1 sites and Smad binding elements located on the IL-11 promoter. Here, we demonstrated that Runx2-c-Jun as well as Runx2-Smad complexes upregulate IL-11 expression. Functional studies identified a significant loss of IL-11 expression in PC3 cells in the presence of the Runx2-HTY mutant protein, a mutation that disrupts Runx2-Smad signaling. In response to TGFβ1 and in the presence of Runx2, we observed a 30-fold induction of IL-11 expression, accompanied by increased c-Jun binding to the IL-11 promoter. Immunoprecipitation and in situ co-localization studies demonstrated that Runx2 and c-Jun form nuclear complexes in PC3 cells. Thus, TGFβ1 signaling induces two independent transcriptional pathways - AP-1 and Runx2. These transcriptional activators converge on IL-11 as a result of Runx2-Smad and Runx2-c-Jun interactions to amplify IL-11 gene expression that, together with Runx2, supports the osteolytic pathology of cancer induced bone disease

    Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein

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    We recently described the Palate Lung Nasal Clone (PLUNC) family of proteins as an extended group of proteins expressed in the upper airways, nose and mouth. Little is known about these proteins, but they are secreted into the airway and nasal lining fluids and saliva where, due to their structural similarity with lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein, they may play a role in the innate immune defence. We now describe the generation and characterisation of novel affinity-purified antibodies to SPLUNC2, and use them to determine the expression of this, the major salivary gland PLUNC. Western blotting showed that the antibodies identified a number of distinct protein bands in saliva, whilst immunohistochemical analysis demonstrated protein expression in serous cells of the major salivary glands and in the ductal lumens as well as in cells of minor mucosal glands. Antibodies directed against distinct epitopes of the protein yielded different staining patterns in both minor and major salivary glands. Using RT-PCR of tissues from the oral cavity, coupled with EST analysis, we showed that the gene undergoes alternative splicing using two 5' non-coding exons, suggesting that the gene is regulated by alternative promoters. Comprehensive RACE analysis using salivary gland RNA as template failed to identify any additional exons. Analysis of saliva showed that SPLUNC2 is subject to N-glycosylation. Thus, our study shows that multiple SPLUNC2 isoforms are found in the oral cavity and suggest that these proteins may be differentially regulated in distinct tissues where they may function in the innate immune response

    Evaluation campaigns and TRECVid

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    The TREC Video Retrieval Evaluation (TRECVid) is an international benchmarking activity to encourage research in video information retrieval by providing a large test collection, uniform scoring procedures, and a forum for organizations interested in comparing their results. TRECVid completed its fifth annual cycle at the end of 2005 and in 2006 TRECVid will involve almost 70 research organizations, universities and other consortia. Throughout its existence, TRECVid has benchmarked both interactive and automatic/manual searching for shots from within a video corpus, automatic detection of a variety of semantic and low-level video features, shot boundary detection and the detection of story boundaries in broadcast TV news. This paper will give an introduction to information retrieval (IR) evaluation from both a user and a system perspective, highlighting that system evaluation is by far the most prevalent type of evaluation carried out. We also include a summary of TRECVid as an example of a system evaluation benchmarking campaign and this allows us to discuss whether such campaigns are a good thing or a bad thing. There are arguments for and against these campaigns and we present some of them in the paper concluding that on balance they have had a very positive impact on research progress

    An open database of productivity in Vietnam's social sciences and humanities for public use

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    This study presents a description of an open database on scientific output of Vietnamese researchers in social sciences and humanities, one that corrects for the shortcomings in current research publication databases such as data duplication, slow update, and a substantial cost of doing science. Here, using scientists’ self-reports, open online sources and cross-checking with Scopus database, we introduce a manual system and its semi-automated version of the database on the profiles of 657 Vietnamese researchers in social sciences and humanities who have published in Scopus-indexed journals from 2008 to 2018. The final system also records 973 foreign co-authors, 1,289 papers, and 789 affiliations. The data collection method, highly applicable for other sources, could be replicated in other developing countries while its content be used in cross-section, multivariate, and network data analyses. The open database is expected to help Vietnam revamp its research capacity and meet the public demand for greater transparency in science management
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