FGF Signaling Is Necessary for the Specification of the Odontogenic Mesenchyme

AbstractTooth development is initiated by signals from the oral ectoderm which induce gene expression required for tooth development in the underlying mesenchyme. In this study, we have used Su5402, an inhibitor of FGF receptor signaling, to analyze the requirement of FGF signaling during early tooth development. We show that FGF signaling is necessary for expression of Pax9, a transcription factor required for development of all teeth, in prospective incisor and molar mesenchyme until E11.0. Expression of the LIM homeobox gene Lhx7 also requires FGF signaling until E11.0 whereas expression of its homologue Lhx6 and the homeobox transcription factor Barx1 already becomes independent of FGF signaling at E10.75. In contrast, ectodermal expression of several genes thought to be important for tooth development was unaffected by the block of FGF signaling. Finally, we show that expression of the TGFβ antagonist Dan in prospective tooth mesenchyme requires ectodermal signals and can be induced by FGF-soaked beads but is maintained in mandibular explants in the absence of FGF signaling. Together, these results demonstrate that FGF signaling is required for development of both molar and incisor teeth and suggest that specification of tooth mesenchyme involves at least two FGF-dependent steps

Ankauf von Staatsanleihen durch die EZB: Wie ist die neue Offenmarktpolitik der Europäischen Zentralbank zu bewerten?

Seit Mai 2010 kauft die Europäische Zentralbank direkt Anleihen privater und öffentlicher Schuldner auf dem Sekundärmarkt. Markus C. Kerber, Technische Universität Berlin, vertritt die Ansicht, dass diese »neue Offenmarktpolitik« der EZB, der Erwerb von Staatsanleihen auf dem Sekundärmarkt, eigentlich nicht erlaubt sei und der Stabilität der Eurozone eher schade. Nach Ansicht von Martin Mandler und Peter Tillmann, Universität Gießen, ist mit dem Programm der EZB ein potentieller Ressourcentransfer an die Krisenstaaten und ihre Gläubiger verbunden, der grundsätzlich nicht in den Aufgabenbereich der Geldpolitik fällt. Dieses Programm in seiner gegenwärtigen Form sei aber nicht alternativlos. Vor dem Hintergrund der »unkonventionellen« Geldpolitik der Zentralbanken rund um den Globus könnte eine andere Ausgestaltung die Risiken solcher Transfers reduzieren.Öffentliche Anleihe, Zentralbank, Öffentliche Schulden, Offenmarktpolitik, EU-Staaten

Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy.

BackgroundMultiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia and dysautonomia. Histopathologically, the hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) within oligodendroglial cells, leading to neuroinflammation, demyelination and neuronal death. Currently, there is no disease-modifying treatment for MSA. In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation.ResultsIn this manuscript, we used the most effective AFFITOPE® (AFF 1) for immunizing MBP-α-syn transgenic mice, a model of MSA that expresses α-syn in oligodendrocytes. Vaccination with AFF 1 resulted in the production of specific anti-α-syn antibodies that crossed into the central nervous system and recognized α-syn aggregates within glial cells. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn, reduced demyelination in neocortex, striatum and corpus callosum, and reduced neurodegeneration. Clearance of α-syn involved activation of microglia and reduced spreading of α-syn to astroglial cells.ConclusionsThis study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies

Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats

<p>Abstract</p> <p>Background</p> <p>Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an <it>in vivo </it>rat model of acute ischemic stroke.</p> <p>Methods</p> <p>Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.</p> <p>Results</p> <p>24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p < 0.001), TNF-α (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls.</p> <p>Conclusions</p> <p>Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.</p

Self-Cognitions in Antisocial Alcohol Dependence and Recovery

Cross-sectional relationships between content and structural properties of the self-concept and alcohol use in young adults with antisocial alcohol dependence (AAD) (n = 24), those in recovery from AAD (n = 18), and controls (n = 23) were examined using the schema model of the self-concept. Persons with AAD had a trend toward fewer positive self-schemas than did controls, and had more negative self-schemas and a trend toward higher interrelatedness than did those in recovery and controls. They also showed evidence of a drinking-related self-schema, whereas those in recovery showed evidence of a recovery-related self-schema. Finally, evidence to support a model using properties of the self-concept to predict high levels of alcohol use was found. These findings provide a beginning empirical foundation for the development of nursing interventions aimed at altering self-structure to prevent the development of and promote recovery from antisocial alcohol dependence.http://deepblue.lib.umich.edu/bitstream/2027.42/65124/1/Corte & Stein 07.pd