TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression

Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner

Major depressive disorder is the main cause of disability worldwide with imperfect treatment options. However, novel therapeutic approaches are currently discussed, from augmentation strategies to novel treatments targeting the immune system or the microbiome-gut-brain axis. Therefore, we examined the potential beneficial effects of minocycline, a tetracycline antibiotic with pleiotropic, immunomodulatory action, alone or as augmentation of escitalopram on behavior, prefrontal microglial density, and the gut microbiome in rats selectively bred for high anxiety-like behavior (HAB). We show that concomitant with their high innate anxiety and depression, HABs have lower microglial numbers in the infralimbic and prelimbic prefrontal cortex and an altered gut microbiota composition compared with controls. Three weeks of minocycline treatment alleviated the depressive-like phenotype, further reduced microglial density, exclusively in male HAB rats, and reduced plasma concentrations of pro-inflammatory cytokines. However, coadministration of escitalopram, which had no effect alone, prevented these minocycline-induced effects. Moreover, minocycline led to a robust shift in cecal microbial composition in both HABs and rats nonselected for anxiety-like behavior. Minocycline markedly increased relative abundance of Lachnospiraceae and Clostridiales Family XIII, families known for their butyrate production, with a corresponding increase and positive correlation in plasma 3-OH-butyrate levels in a trait-dependent manner. Thus, our data suggest that the antidepressant effect of minocycline is sex- and trait-dependent, associated with a reduced microglial number in the prefrontal cortex, and with changes in microbial composition and their metabolites. These results further support the microbiomegut-brain axis as potential target in the treatment of depression

Gene expression profiling for molecular distinction and characterization of laser captured primary lung cancers

<p>Abstract</p> <p>Methods</p> <p>We examined gene expression profiles of tumor cells from 29 untreated patients with lung cancer (10 adenocarcinomas (AC), 10 squamous cell carcinomas (SCC), and 9 small cell lung cancer (SCLC)) in comparison to 5 samples of normal lung tissue (NT). The European and American methodological quality guidelines for microarray experiments were followed, including the stipulated use of laser capture microdissection for separation and purification of the lung cancer tumor cells from surrounding tissue.</p> <p>Results</p> <p>Based on differentially expressed genes, different lung cancer samples could be distinguished from each other and from normal lung tissue using hierarchical clustering. Comparing AC, SCC and SCLC with NT, we found 205, 335 and 404 genes, respectively, that were at least 2-fold differentially expressed (estimated false discovery rate: < 2.6%). Different lung cancer subtypes had distinct molecular phenotypes, which also reflected their biological characteristics. Differentially expressed genes in human lung tumors which may be of relevance in the respective lung cancer subtypes were corroborated by quantitative real-time PCR.</p> <p>Genetic programming (GP) was performed to construct a classifier for distinguishing between AC, SCC, SCLC, and NT. Forty genes, that could be used to correctly classify the tumor or NT samples, have been identified. In addition, all samples from an independent test set of 13 further tumors (AC or SCC) were also correctly classified.</p> <p>Conclusion</p> <p>The data from this research identified potential candidate genes which could be used as the basis for the development of diagnostic tools and lung tumor type-specific targeted therapies.</p

Prospective Nato or EU Membership and Institutional Change in Transition Countries

This paper quantifies the impact of incentives related to potential membership on institutional change as measured by the World Bank Governance Indicators (WBGI). Based on a panel of 25 transition countries for the period from 1996 to 2008 we show that pre-accession incentives provided by EU and NATOclearly matter for institutional development. In addition, path-dependency determined by cultural norms may be overcome by economic liberalization while foreign aid seems to hamper institutional development

Ost-West-Wortschatzvergleiche : maschinell gestützte Untersuchung zum Vokabular von Zeitungstexten aus der BRD und der DDR

"Ost-West-Wortschatzvergleiche" ist der Name eines Forschungsprojekts, das in der früheren Bonner Forschungsstelle des Instituts für deutsche Sprache unter Leitung von Manfred W. Hellmann bearbeitet wurde. Die wichtigsten Projektziele waren: - Bereitstellung eines Textkorpus aus Tageszeitungen der BRD und der DDR als Grundlage ost-west-vergleichender Untersuchungen - Entwicklung kombinierter maschineller und "manueller" lexikographischer Verfahren - Lexikographische Beschreibung von Unterschieden in Wortschatz und Wortgebrauch auf der Grundlage der gespeicherten Texte Die vorliegenden Berichte behandeln die Ansätze und Problemlösungen in diesem Projekt, zu dessen selbstgesetzten Aufgaben es gehörte, "etwas weniger Spekulation und etwas mehr empirisches Wissen" in dieses auch politisch kontrovers diskutierte Thema zu bringen

An der Schwelle zum dritten Jahrtausend: fuer Rainer Hellmann ; von Freunden und Weggefaehrten

SIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, D-21400 Kiel A 213263 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

"Wer gehört dazu?" Überlegungen zur Theorie der Inklusion

Bora A. "Wer gehört dazu?" Überlegungen zur Theorie der Inklusion. In: Hellmann K-U, Schmalz-Bruns R, eds. Theorie der Politik. Niklas Luhmanns politische Soziologie. Suhrkamp-Taschenbuch Wissenschaft. Vol 1583. Frankfurt a. M.: Suhrkamp; 2002: 60-84