30 research outputs found
A Little War That Shook the World:Georgia, Russia, and the Future of the West
In August 2008, Russia shattered the post–Cold War peace in Europe by invading the former Soviet republic of Georgia. Though only days long, that war dashed NATO’s hopes to expand to the Caucasus and sparked fundamental reevaluations of American and Euro- pean Union (EU) relations with Russia. Ronald Asmus’s A Little War That Shook the World is an engaging read that combines the best available history of the war with a broader analysis of the geopolitical forces that led to it
U-Shaped Relation between Plasma Oxytocin Levels and Behavior in the Trust Game
10.1371/journal.pone.0051095PLoS ONE712
Syndecan-1 Enhances Proliferation, Migration and Metastasis of HT-1080 Cells in Cooperation with Syndecan-2
Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects. According to earlier studies, both syndecan-1 and syndecan-2 promote malignancy of HT-1080 human fibrosarcoma cells, by increasing the proliferation rate and the metastatic potential and migratory ability, respectively. To better understand their tumour promoter role in this cell line, syndecan expression levels were modulated in HT-1080 cells and the growth rate, chemotaxis and invasion capacity were studied. For in vivo testing, syndecan-1 overexpressing cells were also inoculated into mice. Overexpression of full length or truncated syndecan-1 lacking the entire ectodomain but containing the four juxtamembrane amino acids promoted proliferation and chemotaxis. These effects were accompanied by a marked increase in syndecan-2 protein expression. The pro-migratory and pro-proliferative effects of truncated syndecan-1 were not observable when syndecan-2 was silenced. Antisense silencing of syndecan-2, but not that of syndecan-1, inhibited cell migration. In vivo, both full length and truncated syndecan-1 increased tumour growth and metastatic rate. Based on our in vitro results, we conclude that the tumour promoter role of syndecan-1 observed in HT-1080 cells is independent of its ectodomain; however, in vivo the presence of the ectodomain further increases tumour proliferation. The enhanced migratory ability induced by syndecan-1 overexpression is mediated by syndecan-2. Overexpression of syndecan-1 also leads to activation of IGF1R and increased expression of Ets-1. These changes were not evident when syndecan-2 was overexpressed. These findings suggest the involvement of IGF1R and Ets-1 in the induction of syndecan-2 synthesis and stimulation of proliferation by syndecan-1. This is the first report demonstrating that syndecan-1 enhances malignancy of a mesenchymal tumour cell line, via induction of syndecan-2 expression
Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration
Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose.
Several studies have combined biomarkers to improve mesothelioma diagnosis, but
with moderate success, and there is a need for new mesothelioma biomarkers. The
tumour is often resistant to treatment and most patients will survive less than a year.
An indicator of patient survival is the tumours growth pattern, which in turn is
influenced by expressed proteoglycans.
In this thesis work, we aim to improve the possibilities to diagnose malignant
mesothelioma by combining biomarkers and by identifying new ones. We also
investigate tumour driving mechanisms with focus on one of these suggested
biomarkers, the cell-bound proteoglycan syndecan-1.
We were able to construct a diagnostic two-step model based on biomarkers in patient
material. By implementing a cut-off level and thereafter focusing on unresolved patients
we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased
the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we
used mass spectrometry to find new biomarkers. We identified and validated galectin-1,
which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II).
In the same study, we were also the first to describe aldo-keto reductase 1B10 as a
novel prognostic mesothelioma biomarker.
Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how
higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma.
This was verified in paper II when syndecan-1 was identified as downregulated in fluids
from mesothelioma patients compared to lung cancer patients. Paper III and paper IV
focus on this proteoglycan.
Malignant cell lines transfected with syndecan-1 and various truncated forms of
syndecan-1 affected adhesion and migration, which are key features of cancer invasion
(paper III). The results showed a domain- and cell type specific effect on the cells’
motility. Regulating syndecan-1 levels and analysing the global gene expression of
mesothelioma cells made it evident that this proteoglycan has a strong influence on
transforming growth factor β signalling and several growth factor pathways (paper IV).
Links to cell migration and proliferation were furthermore identified, along with
glycosaminoglycan modifying enzymes. These results can shed light on the complex role
of syndecan-1 in invasion and growth of malignant mesenchymal cells.
Taken together, this thesis work describes a complement to conventional mesothelioma
diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker
syndecan-1 was shown to have an effect on cell motility and proliferation. These results
increase our understanding of this aggressive malignancy
Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.
Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events
Diversionary temptations : presidential incentives and the political use of force
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Political Science, 2003.Includes bibliographical references (v. 2, leaves 407-420).This dissertation assesses U.S. presidents' incentives for diversionary war. The political benefits of the use of force were measured and compared to the benefits of other dramatic foreign policy activities. Gains from force were modest, not unique, and discounted in many circumstances of political need. Statistical tests measured the changes in presidential approval ratings following uses of force, major diplomatic events, presidential speeches, and foreign travel by presidents, in the period 1953-2000. Historical sources and newspaper archives were used to identify and characterize uses of force and diplomatic events. Uses of force provide only modest and short-lived approval gains (average 6% increase with 3 month half life for major uses). Approval changes were greater with more media coverage, Congressional support, or popular goals (e.g., protecting American lives, not humanitarian intervention). Approval gains were higher during recessions, but losses occurred when prior approval was low for non-economic reasons (e.g., scandals). Diplomatic events produced slightly smaller benefits, conditioned by similar variables except for retaining their popularity during scandals. Foreign travel and speeches had little impact. The frequency of presidential activities changes in response to political variables, in ways that are consistent with maximization of political benefits. Uses of force became slightly more common during recessions, less common when approval was low for non-economic reasons.(cont.) Elections reduced the rate of all activities. These results may explain previous negative findings for U.S. diversionary war: presidential incentives for diversionary force are weak because potential gains are small, other tools are available, and they are discounted during times of need. Diversionary use of force would be attractive during economic slowdowns, however.by David T. Burbach.Ph.D