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The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many glycosaminoglycan chains, that provide the basis for the viscoelastic properties necessary for load distributi
Background/Aims: Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. M
The urokinase-type plasminogen activator receptor (uPAR) is a non-integrin vitronectin (VN) cell adhesion receptor linked to the plasma membrane by a glycolipid anchor. Through structure-function analyses of uPAR, VN and integrins, we document that uPAR-mediated cell adhesion to VN triggers a novel type of integrin signalling that is independent of integrin-matrix engagement. The signalling is ful
Protein kinase C iota (PKCι), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCι is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCι is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) c
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role
TGF-β can act as a tumor suppressor at early stages of cancer progression and as a tumor promoter at later stages. The E3 ubiquitin ligase Arkadia (RNF111) is a critical component of the TGF-β signaling pathway, being required for a subset of responses, those mediated by Smad3-Smad4 complexes. It acts by mediating ligand-induced degradation of Ski and SnoN (SKIL), which are 2 potent transcriptiona
Cancer cells can move through tissues in a variety of different ways. In some cases, an epithelial-to-mesenchymal transition enables cancer cells to acquire fibroblast-like migratory properties. However, it is also becoming apparent that some cancer cells move in an amoeboid way similar to leukocytes. This theme will be the focus of the review, where we will discuss the similarities and difference
BACKGROUND: The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex forme
The extracellular matrix (ECM) is a complex structural entity surrounding and supporting cells present in all tissue and organs. Cell-matrix interactions play fundamental roles during embryonic development, morphogenesis, tissue homoeostasis, wound healing, and tumourigenesis. Cell-matrix communication is kept in balance by physical contact and by transmembrane integrin receptors providing the dyn
To search for functional links between glycosylphosphatidylinositol (GPI) protein monomer-oligomer exchange and membrane dynamics and confinement, we studied urokinase plasminogen activator (uPA) receptor (uPAR), a GPI receptor involved in the regulation of cell adhesion, migration, and proliferation. Using a functionally active fluorescent protein-uPAR in live cells, we analyzed the effect that e
Expression of the membrane receptor uPAR induces profound changes in cell morphology and migration, and its expression correlates with the malignant phenotype of cancers. To identify the molecular interactions essential for uPAR function in these processes, we carried out a complete functional alanine scan of uPAR in HEK293 cells. Of the 255 mutant receptors characterized, 34 failed to induce chan
Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this study, the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was investigated. T
OBJECTIVES: To determine the prevalence of TT virus (TTV) in a population of Danish hemodialysis patients and evaluate possible relations between TTV infection and elevated levels of C-reactive protein (CRP) and hypo-response to treatment with erythropoietin (EPO).MATERIAL AND METHODS: Patients on maintenance hemodialysis at a single center were invited to participate. Demographic and clinical dat
PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART).METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples ta
This study examines perceptions of humour and happiness in a world where NPM ideas have a profound influence on many aspects of everyday living. The researchers interviewed comedians and their circle of co-workers at comedy festivals. Comedians seek to make us laugh, but this paper examines whether they have a serious message, too. This research reveals comedians as critical thinkers, as edge-workThis study examines perceptions of humour and happiness in a world where NPM ideas have a profound influence on many aspects of everyday living. The researchers interviewed comedians and their circle of co-workers at comedy festivals. Comedians seek to make us laugh, but this paper examines whether they have a serious message, too. This research reveals comedians as critical thinkers, as edge-work
The crustacean optic neuropiles, the lamina ganglionaris and especially the medulla externa, show a specific pattern of green fluorescence with the fluorescence histochemical method of Falck-Hillarp. Normally, only the terminals and the cell bodies fluoresce, but in reserpine-treated animals exogenous catecholamines are taken up by the whole adrenergic neuron and are thus visualized as a whole. In
It is clear that technology is a key driver of economic growth. Much less clear is where new technologies are produced and how the geography of U.S. invention has changed over the last two hundred years. Patent data report the geography, history, and technological characteristics of invention. However, those data have only recently become available in digital form and at the present time there exi
Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are two frequent causes of dementia that share both clinical and neuropathological features. Common to both disorders are the neurofibrillary tangles consisting of aggregations of hyperphosphorylated tau protein. Recently, a number of different pathogenic mutations in the tau gene have been identified in families with FTD and parkinsonism
The funnel metadynamics method enables rigorous calculation of the potential of mean force along an arbitrary binding path and thereby evaluation of the absolute binding free energy. A problem of such physical paths is that the mechanism characterizing the binding process is not always obvious. In particular, it might involve reorganization of the solvent in the binding site, which is not easily c
