Das Konzept der quattromodalen Knoten

Die Verknüpfung der vier Verkehrsträger Straße, Schiene, Wasserstraße und Luft an einem quattromodalen Güterverkehrsknoten ist derzeit noch ein Randthema mit vielen Unbekannten. Das österreichische Forschungsprojekt „Q4“ widmet sich dieser Wissenslücke und stellt das Potential sowie die Grenzen quattromodaler Knoten im Güterverkehr in den Fokus der Forschung. Im Zuge dessen werden beispielhaft Möglichkeiten der Umsetzung für den österreichischen Zentralraum Linz-Wels-Steyr und die Metropolregion Wien aufgezeigt

Aadh2p: an Arxula adeninivorans alcohol dehydrogenase involved in the first step of the 1-butanol degradation pathway

Additional file 3: Figures S3. Key compounds of the ß-oxidation - microarray studies. The SBGN style metabolic network depicts reversible (double headed arrow) and irreversible (single headed arrow) reactions catalyzed by the corresponding enzymes (rectangular square). Enzymes are enriched with color-coded fold change values of time resolved expression data of the respective genes. The colors represent upregulation (blue) and downregulation (red) of genes in cells shifted to medium containing 1-butanol as the carbon source compared to cells grown with glucose. Metabolites or enzymes occurring multiple times in the metabolic network are decorated with a clone marker (e.g. CoA) (produced using VANTED [2, 3])

Low spinophilin expression enhances aggressive biological behavior of breast cancer

Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24-3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer

RNAi-Mediated c-Rel Silencing Leads to Apoptosis of B Cell Tumor Cells and Suppresses Antigenic Immune Response In Vivo

c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases

Resolution of inflammation: what Controls its Onset?

The authors would like to acknowledge the funding agencies, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Comissão de Aperfeiçoamento de Pessoal do Ensino Superior (CAPES, Brazil), Fundação do Amparo a Pesquisa de Minas Gerais (FAPEMIG, Brazil), Instituto Nacional de Ciência e Tecnologia (INCT in Dengue), and the European Community’s Seventh Framework Programme (FP7-2007-2013, Timer consortium) under grant agreement HEALTH-F4-2011-281608. MP acknowledges funding from the Wellcome Trust (program 086867/Z/08), the Medical Research Council UK (MR/K013068/1), and the William Harvey Research Foundation

Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation

<div><p>Background</p><p>Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 μM) also promote proliferation of bone cancer cells <i>in vitro</i>. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective <i>in vitro</i> and <i>in vivo</i>. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts.</p><p>Methods</p><p>Thus, an initial screening based on cell cycle phase alterations, estrogen (ER) and vitamin D receptor (VDR) expression, live cell metabolic monitoring, and metabolomics were performed.</p><p>Results</p><p>Exposure to the combination of 100 μM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERß and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells. In order to identify the underlying cellular mechanisms in the MG-63 cell line, metabolic profiling via GC/MS technology was conducted. Combined treatment significantly influenced lipids and amino acids preferably, whereas metabolites of the energy metabolism were not altered. The comparative analysis of the log2-ratios revealed that after combined treatment only the metabolite ethanolamine was highly up-regulated. This is the result: a strong overexpression (350%) of the enzyme sphingosine-1-phosphate lyase (SGPL1), which irreversibly degrades sphingosine-1-phosphate (S1P), thereby, generating ethanolamine. S1P production and secretion is associated with an increased capability of migration and invasion of cancer cells.</p><p>Conclusion</p><p>From these results can be concluded that the tumor promoting effect of high concentrations of genistein in immature osteosarcoma cells is reduced by the co-administration of calcitriol, primarily by the breakdown of S1P. It should be tested whether this anti-metastatic pathway can be stimulated by combined treatment also in metastatic xenograft mice models.</p></div