Guaraná (Paullinia cupana) as a commercial crop in Brazilian Amazonia

Guaraná (Paullinia cupana) is a woody vine or sprawling shrub native to the central Amazon Basin. The seeds are commercially produced on some 6,000 ha in the state of Amazonas near Manaus. The principal article of commerce is an amber-colored, carbonated soft drink. It is also widely used as a high caffeine stimulant and in local medicines. The plant is monoecious and is damaged by a number of diseases, the most severe being anthracnose. Prospects are excellent for greatly expanded international markets.     

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.     

Studies on the lipid dependency and mechanism of the translocation of the mitochondrial precursor protein apocytochrome c across model membranes

The lipid dependency of apocytochrome c binding to model membranes and of the translocation of the precursor protein across these membranes was studied by using large unilamellar, trypsin-containing vesicles. These vesicles were improved with respect to those used in a previous article (Rietveld, A., and de Kruijff, B. (1984) J. Biol. Chem. 259, 6704-6706), in the sense that a lower amount of trypsin was enclosed. In mixed egg phosphatidylcholine/bovine brain phosphatidylserine vesicles, both the Kd of apocytochrome c binding (about 20 microM) and the number of phosphatidylserine molecules interacting with the protein was found to be constant. When the phosphatidylserine fraction in the vesicles is more than 15-30% apocytochrome c addition results in the exposure of (a part of) the protein to the internal, trypsin-containing vesicle medium, which process we conceive as a translocation event. Also the interaction of apocytochrome c with vesicles composed of phosphatidylcholine and another acidic phospholipid in a 1:1 ratio, leads to the translocation of the protein across the model membrane. The affinity of this binding was found to be in the order cardiolipin greater than phosphatidylglycerol greater than phosphatidylinositol greater than phosphatidylserine. By varying the lipid composition of the vesicles, it could be demonstrated that the translocation requires a fluid bilayer. In addition, protein specificity was shown for the translocation process. Although apocytochrome c-lipid interaction causes vesicle aggregation, fusion by lipid mixing could not be detected. Due to the apocytochrome c-lipid interaction also, protein aggregates and oligomers have been formed. These results will be discussed in the light of a model for translocation of a precursor protein across a model membrane. The relevance for the mitochondrial system will also be discussed.     

TBCD Links Centriologenesis,Spindle Microtubule Dynamics,and Midbody Abscission in Human Cells

Microtubule-organizing centers recruit α- and β-tubulin polypeptides for microtubule nucleation. Tubulin synthesis is complex, requiring five specific cofactors, designated tubulin cofactors (TBCs) A–E, which contribute to various aspects of microtubule dynamics in vivo. Here, we show that tubulin cofactor D (TBCD) is concentrated at the centrosome and midbody, where it participates in centriologenesis, spindle organization, and cell abscission. TBCD exhibits a cell-cycle-specific pattern, localizing on the daughter centriole at G1 and on procentrioles by S, and disappearing from older centrioles at telophase as the protein is recruited to the midbody. Our data show that TBCD overexpression results in microtubule release from the centrosome and G1 arrest, whereas its depletion produces mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis. TBCD is recruited to the centriole replication site at the onset of the centrosome duplication cycle. A role in centriologenesis is further supported in differentiating ciliated cells, where TBCD is organized into “centriolar rosettes”. These data suggest that TBCD participates in both canonical and de novo centriolar assembly pathways.