Greening des Innovationssystems?

Das Thema Umwelt und Innovation läßt sich von zwei Seiten angehen. Die innovationsökonomische Literatur legt als Ausgangspunkt das nationale Innovationssystem nahe, dem eine Schlüsselrolle für die Leistungsfähigkeit hochentwickelter Volkswirtschaften beigemessen wird. Die Umweltökonomie nähert sich den Umweltinnovationen häufig von der Instrumentenseite. Beide Stränge werden meist jedoch nicht miteinander verknüpft. Ein Forschungsprojekt an der Fachhochschule für Wirtschaft versucht, diese Brücke zu schlagen

A Helminth Protease Inhibitor Modulates the Lipopolysaccharide-Induced Proinflammatory Phenotype of Microglia in vitro

Objective: The aim of this study was to examine whether the natural protease inhibitor Av-cystatin (rAv17) of the parasitic nematode Acanthocheilonema viteae exerts anti-inflammatory effects in an in vitro model of lipopolysaccharide (LPS)-activated microglia. Methods: Primary microglia were harvested from the brains of 2-day-old Wistar rats and cultured with or without rAv17 (250 nM). After 6 and 24 h the release of nitric oxide (Griess reagent) and TNF-α (ELISA) was measured in the supernatant. Real-time PCR was performed after 2, 6 and 24 h of culture to measure the mRNA expression of IL-1β, IL-6, TNF-α, COX-2, iNOS and IL-10. To address the involved signaling pathways, nuclear NF-ĸB translocation was visualized by immunocytochemistry. Morphological changes of microglia were analyzed by Coomassie blue staining. Differences between groups were calculated using one-way ANOVA with Bonferroni's post hoc test. Results: Morphological analysis indicated that LPS-induced microglial transformation towards an amoeboid morphology is inhibited by rAv17. Av-cystatin caused a time-dependent downregulation of proinflammatory cytokines, iNOS and COX-2 mRNA expression, respectively. This was paralleled by an upregulated expression of IL-10 in resting as well as in LPS-stimulated microglia. Av-cystatin reduced the release of NO and TNF-α in the culture supernatant. Immunocytochemical staining demonstrated an attenuated translocation of NF-ĸB by Av-cystatin in response to LPS. In addition, Western blot analysis revealed a rAv17-dependent reduction of the LPS-induced ERK1/2-pathway activation. Conclusion: The parasite-derived secretion product Av-cystatin inhibits proinflammatory mechanisms of LPS-induced microglia with IL-10, a potential key mediator.Peer Reviewe

The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma

Peripheral T cell lymphomas (PTCLs) are highly aggressive malignancies with poor prognosis. Their molecular pathogenesis is not well understood and small animal models for the disease are lacking. Recently, the chromosomal translocation t(5;9)(q33;q22) generating the interleukin-2 (IL-2)–inducible T cell kinase (ITK)–spleen tyrosine kinase (SYK) fusion tyrosine kinase was identified as a recurrent event in PTCL. We show that ITK-SYK associates constitutively with lipid rafts in T cells and triggers antigen-independent phosphorylation of T cell receptor (TCR)–proximal proteins. These events lead to activation of downstream pathways and acute cellular outcomes that correspond to regular TCR ligation, including up-regulation of CD69 or production of IL-2 in vitro or deletion of thymocytes and activation of peripheral T cells in vivo. Ultimately, conditional expression of patient-derived ITK-SYK in mice induces highly malignant PTCLs with 100% penetrance that resemble the human disease. Our work demonstrates that constitutively enforced antigen receptor signaling can, in principle, act as a powerful oncogenic driver. Moreover, we establish a robust clinically relevant and genetically tractable model of human PTCL

Imprinted CDKN1C Is a Tumor Suppressor in Rhabdoid Tumor and Activated by Restoration of SMARCB1 and Histone Deacetylase Inhibitors

SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor

The Survey of Water and Ammonia in the Galactic Center (SWAG): Molecular Cloud Evolution in the Central Molecular Zone

The Survey of Water and Ammonia in the Galactic Center (SWAG) covers the Central Molecular Zone (CMZ) of the Milky Way at frequencies between 21.2 and 25.4 GHz obtained at the Australia Telescope Compact Array at $\sim 0.9$ pc spatial and $\sim 2.0$ km s$^{-1}$ spectral resolution. In this paper, we present data on the inner $\sim 250$ pc ($1.4^\circ$) between Sgr C and Sgr B2. We focus on the hyperfine structure of the metastable ammonia inversion lines (J,K) = (1,1) - (6,6) to derive column density, kinematics, opacity and kinetic gas temperature. In the CMZ molecular clouds, we find typical line widths of $8-16$ km s$^{-1}$ and extended regions of optically thick ($\tau > 1$) emission. Two components in kinetic temperature are detected at $25-50$ K and $60-100$ K, both being significantly hotter than dust temperatures throughout the CMZ. We discuss the physical state of the CMZ gas as traced by ammonia in the context of the orbital model by Kruijssen et al. (2015) that interprets the observed distribution as a stream of molecular clouds following an open eccentric orbit. This allows us to statistically investigate the time dependencies of gas temperature, column density and line width. We find heating rates between $\sim 50$ and $\sim 100$ K Myr$^{-1}$ along the stream orbit. No strong signs of time dependence are found for column density or line width. These quantities are likely dominated by cloud-to-cloud variations. Our results qualitatively match the predictions of the current model of tidal triggering of cloud collapse, orbital kinematics and the observation of an evolutionary sequence of increasing star formation activity with orbital phase

How Nature Brings Proteins to Life: Conformations and Dynamics of a HAMP Domain, Channelrhodopsin-2, and the Human CCAse Studied by EPR Spectroscopy

In this work, we studied three proteins from three different organisms by EPR spectroscopy: NpHtrII is part of the phototaxis system found in halophilic archaea, ChR2 is a cation-selective channel isolated from a green alga, and HsaCCA is an enzyme involved in the protein biosynthesis of humans. The goal was to identify characteristic conformations and dynamics in each of the studied proteins that were linked to their specific functions. The scientific disciplines employed in this work include biochemistry (site-directed spin-labeling), bioinformatics (data analysis, molecular modeling), informatics (device control, software development), molecular biology (mutagenesis, transformation, heterologous protein expression, protein purification, protein characterization), and physics (EPR spectroscopy, optical spectroscopy, experimental assembly). The experimental results show a strong interdependence between protein structure, conformers, dynamics, and function. Hydrogen bonds, although being a transient electrostatic attraction between polar molecules, are the key molecular interactions required for the conservation of protein functionality: Hydrogen bond networks in NpSRII and ChR2 stabilize the helix bundles, and hydrogen bond networks in HsaCCA mediate interdomain flexibility. However, the resulting structural alterations observed in our proteins manifest on a much larger scale: We have detected changes in the protein backbone mobility of the HAMP2 domain in NpHtrII after signaling. We have discovered the TMH B movement in ChR2 accompanying channel opening. And we have documented a substrate-dependent motion of the head domain in HsaCCA during catalysis