Phylogenetic relationships of the downy mildews (Peronosporales) and related groups based on nuclear large subunit ribosomal DNA sequences.

In order to investigate phylogenetic relationships of the Peronosporomycetes (Oomycetes), nuclear large subunit ribosomal DNA sequences containing the D1 and D2 region were analyzed of 92 species belonging to the orders Peronosporales, Pythiales, Leptomitales, Rhipidiales, Saprolegniales and Sclerosporales. The data were analyzed applying methods of neighbor-joining as well as maximum parsimony, both statistically supported using the bootstrap method. The results confirm the major division between the Pythiales and Peronosporales on the one hand and the Saprolegniales, Leptomitales, and Rhipidiales on the other. The Sclerosporales were shown to be polyphyletic; while Sclerosporaceae are nested within the Peronosporaceae, the Verrucalvaceae are merged within the Saprolegniales. Within the Peronosporomycetidae, Pythiales as well as Peronosporales as currently defined are polyphyletic. The well supported Albugo clade appears to be the most basal lineage, followed by a Pythium-Lagenidium clade. The third, highly supported clade comprises the Peronosporaceae together with Sclerospora, Phytophthora, and Peronophythora. Peronophythora is placed within Phytophthora, indicating that both genera should be merged. Bremiella seems to be polyphyletic within the genus Plasmopara, suggesting a transfer to Plasmopara. The species of Peronospora do not appear as a monophyletic group. Peronospora species growing on Brassicaceae form a highly supported clade.

SAR of novel biarylmethylamine dopamine D4 receptor ligands.

SAR for a novel series of dopamine D4 receptor ligands is shown. Very selective, highly potent compounds like 1-(2-pyrimidinyl)-4-(3-(3-thienyl)-benzyl)-piperazine (5f) and 2-(4-(1-fluorenylmethyl)-1-piperazinyl)-pyrimidine (8c) were obtained.

2',3'-cyclic nucleotide 3'-phosphodiesterase: a novel candidate autoantigen in demyelinating diseases.

Autoaggressive T-cells specific for myelin proteins like proteolipid protein (PLP) and myelin basic protein (MBP) are thought to play a major role in the pathogenesis of demyelinating diseases of the central nervous system (CNS). 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is the third most abundant myelin protein in the CNS. Due to lack of supply with enough CNPase of sufficient purity its immunologic properties have not been studied yet. We subcloned a human CNPase cDNA and expressed human recombinant CNPase (rh-CNPase) in E. coli. Purification of the protein was achieved by Ni(2+)-chelating chromatography. Furthermore we describe for the first time several rh-CNPase specific T-cell lines from a multiple sclerosis patient and a healthy control.

The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis.

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) the cytokines tumour necrosis factor-alpha (TNF), lymphotoxin-alpha (LT), and interferon-gamma (IFN-gamma) are of central pathogenetic importance. A therapy capable of stopping neurological deterioration in MS patients is not yet available. Here, we report that rolipram, a selective type IV phosphodiesterase inhibitor, stereospecifically suppresses the production of TNF/LT and less strongly also IFN-gamma in human and rat auto-reactive T cells. Moreover, we show that rolipram is an effective treatment for EAE. Rolipram has extensively been studied in humans for the treatment of depression, but has not yet been marketed. The data presented here identify rolipram as potential therapy for multiple sclerosis and provoke the immediate initiation of clinical trials.