University of Göttingen

About: University of Göttingen is a education organization based out in Göttingen, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 43851 authors who have published 86318 publications receiving 3010295 citations. The organization is also known as: Georg-August-Universität Göttingen & Universität Göttingen.

The δC Isoform of CaMKII Is Activated in Cardiac Hypertrophy and Induces Dilated Cardiomyopathy and Heart Failure

Abstract: Recent studies have demonstrated that transgenic (TG) expression of either Ca 2+ /calmodulin-dependent protein kinase IV (CaMKIV) or CaMKIIδ B , both of which localize to the nucleus, induces cardiac hypertrophy. However, CaMKIV is not present in heart, and cardiomyocytes express not only the nuclear CaMKIIδ B but also a cytoplasmic isoform, CaMKIIδ C . In the present study, we demonstrate that expression of the δ C isoform of CaMKII is selectively increased and its phosphorylation elevated as early as 2 days and continuously for up to 7 days after pressure overload. To determine whether enhanced activity of this cytoplasmic δ C isoform of CaMKII can lead to phosphorylation of Ca 2+ regulatory proteins and induce hypertrophy, we generated TG mice that expressed the δ C isoform of CaMKII. Immunocytochemical staining demonstrated that the expressed transgene is confined to the cytoplasm of cardiomyocytes isolated from these mice. These mice develop a dilated cardiomyopathy with up to a 65% decrease in fractional shortening and die prematurely. Isolated myocytes are enlarged and exhibit reduced contractility and altered Ca 2+ handling. Phosphorylation of the ryanodine receptor (RyR) at a CaMKII site is increased even before development of heart failure, and CaMKII is found associated with the RyR in immunoprecipitates from the CaMKII TG mice. Phosphorylation of phospholamban is also increased specifically at the CaMKII but not at the PKA phosphorylation site. These findings are the first to demonstrate that CaMKIIδ C can mediate phosphorylation of Ca 2+ regulatory proteins in vivo and provide evidence for the involvement of CaMKIIδ C activation in the pathogenesis of dilated cardiomyopathy and heart failure.

A novel vascular endothelial growth factor encoded by Orf virus, VEGF‐E, mediates angiogenesis via signalling through VEGFR‐2 (KDR) but not VEGFR‐1 (Flt‐1) receptor tyrosine kinases

Abstract: The different members of the vascular endothelial growth factor (VEGF) family act as key regulators of endothelial cell function controlling vasculogenesis, angiogenesis, vascular permeability and endothelial cell survival. In this study, we have functionally characterized a novel member of the VEGF family, designated VEGF-E. VEGF-E sequences are encoded by the parapoxvirus Orf virus (OV). They carry the characteristic cysteine knot motif present in all mammalian VEGFs, while forming a microheterogenic group distinct from previously described members of this family. VEGF-E was expressed as the native protein in mammalian cells or as a recombinant protein in Escherichia coli and was shown to act as a heat-stable, secreted dimer. VEGF-E and VEGF-A were found to possess similar bioactivities, i.e. both factors stimulate the release of tissue factor (TF), the proliferation, chemotaxis and sprouting of cultured vascular endothelial cells in vitro and angiogenesis in vivo. Like VEGF-A, VEGF-E was found to bind with high affinity to VEGF receptor-2 (KDR) resulting in receptor autophosphorylation and a biphasic rise in free intracellular Ca2+ concentration, whilst in contrast to VEGF-A, VEGF-E did not bind to VEGF receptor-1 (Flt-1). VEGF-E is thus a potent angiogenic factor selectively binding to VEGF receptor-2. These data strongly indicate that activation of VEGF receptor-2 alone can efficiently stimulate angiogenesis.

Innate immune memory in the brain shapes neurological disease hallmarks

Abstract: Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished—training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer’s pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.

Methanococcus jannaschii sp. nov., an extremely thermophilic methanogen from a submarine hydrothermal vent

Abstract: A new extremely thermophilic methane-producing bacterium was isolated from a submarine hydrothermal vent sample collected by a research team from the Woods Hole Oceanographic Institution using the manned submersible ALVIN. The sample was obtained from the base of a “white smoker” chimney on the East Pacific Rise at 20° 50′ N latitude and 109° 06′ W longitude at a depth of 2600 m. The isolate was a motile irregular coccus with an osmotically fragile cell wall and a complex flagellar system. In defined medium with 80% H2 and 20% CO2, the isolate had a doubling time of 26 min at 85° C. The pH range for growth was 5.2 to 7.0 with an optimum near 6.0. NaCl was required for growth with an optimum of 2 to 3% (w/v). The mol % G+C was 31%. In cell-free extracts, methane formation from methylcoenzyme M was temperature-dependent, and H2 or formate served as electron donors. Methane formation from H2 and CO2 occurred at a much lower rate. Oligonucleotide cataloging of the 16S ribosomal RNA established the isolate as a new species of the genus Methanococcus and the name Methanococcus jannaschii is proposed. The isolation of M. jannaschii from a submarine hydrothermal vent provides additional evidence for biogenic production of CH4 from these deep-sea environments.

Phylogeny and evolution of ferns (monilophytes) with a focus on the early leptosporangiate divergences

Abstract: The phylogenetic structure of ferns (5 monilophytes) is explored here, with a special focus on the early divergences among leptosporangiate lineages. Despite considerable progress in our understanding of fern relationships, a rigorous and comprehensive analysis of the early leptosporangiate divergences was lacking. Therefore, a data set was designed here to include critical taxa that were not included in earlier studies. More than 5000 bp from the plastid (rbcL, atpB, rps4) and the nuclear (18S rDNA) genomes were sequenced for 62 taxa. Phylogenetic analyses of these data (1) confirm that Osmundaceae are sister to the rest of the leptosporangiates, (2) resolve a diverse set of ferns formerly thought to be a subsequent grade as possibly monophyletic (((Dipteridaceae, Matoniaceae), Gleicheniaceae), Hymenophyllaceae), and (3) place schizaeoid ferns as sister to a large clade of ‘‘core leptosporangiates’’ that includes heterosporous ferns, tree ferns, and polypods. Divergence time estimates for ferns are reported from penalized likelihood analyses of our molecular data, with constraints from a reassessment of the fossil record.