Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice. CONCLUSIONS: Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI

Witten spinors on maximal, conformally flat hypersurfaces

The boundary conditions that exclude zeros of the solutions of the Witten equation (and hence guarantee the existence of a 3-frame satisfying the so-called special orthonormal frame gauge conditions) are investigated. We determine the general form of the conformally invariant boundary conditions for the Witten equation, and find the boundary conditions that characterize the constant and the conformally constant spinor fields among the solutions of the Witten equations on compact domains in extrinsically and intrinsically flat, and on maximal, intrinsically globally conformally flat spacelike hypersurfaces, respectively. We also provide a number of exact solutions of the Witten equation with various boundary conditions (both at infinity and on inner or outer boundaries) that single out nowhere vanishing spinor fields on the flat, non-extreme Reissner--Nordstr\"om and Brill--Lindquist data sets. Our examples show that there is an interplay between the boundary conditions, the global topology of the hypersurface and the existence/non-existence of zeros of the solutions of the Witten equation.Comment: 23 pages, typos corrected, final version, accepted in Class. Quantum Gra

Natur und Leben in der deutschen Geistesgeschichte

I. Natur und Leben in der Geistesgeschicht

Gott, Natur, Kunst und Geschichte: Schelling zwischen Identitätsphilosophie und Freiheitsschrift

Die Beiträge thematisieren die philosophische Entwicklung Friedrich Wilhelm Joseph Schellings (1775–1854) im ersten Jahrzehnt des 19. Jahrhunderts. Schelling hatte 1801 einen umfassenden Entwurf einer systematischen Philosophie vorgelegt, in dem die gesamte Natur und die gesamte Geisteswelt als Erscheinungen ein und desselben Prinzips verstanden werden. Im Jahre 1809 legte er mit der Schrift »Philosophische Untersuchungen über das Wesen der menschlichen Freiheit« eine Konzeption vor, die dem Systementwurf von 1801 scheinbar widerspricht. In der Schelling-Forschung ist diese Entwicklungsphase zwischen Identitätsphilosophie und Freiheitsschrift heftig umstritten. Die Beiträge des Bandes machen nun erstmals die Entwicklung der Philosophie Schellings hin zur Freiheitsschrift als eine kontinuierliche Weiterentwicklung seines Ansatzes von 1801 deutlich. Damit kommt es zu einer Klärung wichtiger werkgeschichtlicher Entwicklungsprobleme in der Philosophie Schellings, die weit über den engeren Bereich der Schelling-Forschung von Interesse sind

Low prevalence of lactase persistence in bronze age europe indicates ongoing strong selection over the last 3,000 years

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic- Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years

Report of the ICES WKROUNDMP 2011 / STECF EWG 11-07. Evaluation and Impact As-sessment of Management Plans PT II

A joint ICES / STECF meeting was held in Hamburg 20-24 June 2011, to prepare an Evaluation of multi-annual plans for cod in Kattegat, North Sea, Irish Sea and West of Scotland. The meeting involved STECF, ICES scientists dealing with Economy and Biology and included Observers (Commission staff, Managers, Stakeholders). Three separate reports to the STECF were prepared by the EWG-11-07, one on the Impact Assessment of Southern hake, Nephrops and Angler fish (EWG-11-07c) and another on the Impact Assessments for Baltic cod (EWG 11-07a) and this third on the Evaluation of Cod in Kattegat, North Sea, West of Scotland and Irish Sea (EWG-11-07b) and clari-fication of Advice on NS whiting.JRC.G.4-Maritime affair