Purealidin A,a new cytotoxic bromotyrosine-derived alkaloid from the Okinawan marine spongePsammaplysilla purea

Summary A new bromotyrosine-derived alkaloid with antileukemic activity, purealidin A (5), has been isolated from the Okinawan marine spongePsammaplysilla purea and its chemical structure elucidated on the basis of the spectroscopic data.     

A small GTP-binding protein dissociates from synaptic vesicles during exocytosis.

Low-molecular-weight GTP-binding proteins are strong candidates for regulators of membrane traffic. In yeast, mutations in the sec4 or ypt1 genes encoding small GTP-binding proteins inhibit constitutive membrane flow at the plasma membrane or Golgi complex, respectively. It has been suggested that membrane fusion-fission events are regulated by cycling of small GTP-binding proteins between a membrane-bound and free state, but although most of these small proteins are found in both soluble and tightly membrane-bound forms, there is no direct evidence to support such cycling. In rat brain a small GTP-binding protein, rab3A, is exclusively associated with synaptic vesicles, the secretory organelles of nerve terminals. Here we use isolated nerve terminals to study the fate of rab3A during synaptic vesicle exocytosis. We find that rab3A dissociates quantitatively from the vesicle membrane after Ca2(+)-dependent exocytosis and that this dissociation is partially reversible during recovery after stimulation. These results are direct evidence for an association-dissociation cycle of a small GTP-binding protein during traffic of its host membrane.     

Face Recognition Based on Support Vector Machine and Nearest Neighbor Classifier

Support vector machine (SVM), as a novel approach in pattern recognition, has demonstrated a success in face detection and face recognition. In this paper, a face recognition approach based on the SVM classifier with the nearest neighbor classifier (NNC) is proposed. The principal component analysis (PCA) is used to reduce the dimension and extract features. Then one-against-all stratedy is used to train the SVM classifiers. At the testing stage, we propose an al-     

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.     

Structure of the detoxification catalyst mercuric ion reductase from Bacillus sp. strain RC607

Several hundred million tons of toxic mercurials are dispersed in the biosphere. Microbes can detoxify organo-mercurials and mercury salts through sequential action of two enzymes, organomercury lyase and mercuric ion reductase (MerA). The latter, a homodimer with homology to the FAD-dependent disulphide oxidoreductases, catalyses the reaction NADPH + Hg(II)----NADP+ + H+ + Hg(0), one of the very rare enzymic reactions with metal substrates. Human glutathione reductase serves as a reference molecule for FAD-dependent disulphide reductases and between its primary structure and that of MerA from Tn501 (Pseudomonas), Tn21 (Shigella), p1258 (Staphylococcus) and Bacillus, 25-30% of the residues have been conserved. All MerAs have a C-terminal extension about 15 residues long but have very varied N termini. Although the enzyme from Streptomyces lividans has no addition, from Pseudomonas aeruginosa Tn501 and Bacillus sp. strain RC607 it has one and two copies respectively of a domain of 80-85 residues, highly homologous to MerP, the periplasmic component of proteins encoded by the mer operon. These domains can be proteolytically cleaved off without changing the catalytic efficiency. We report here the crystal structure of MerA from the Gram-positive bacterium Bacillus sp. strain RC607. Analysis of its complexes with nicotinamide dinucleotide substrates and the inhibitor Cd(II) reveals how limited structural changes enable an enzyme to accept as substrate what used to be a dangerous inhibitor. Knowledge of the mode of mercury ligation is a prerequisite for understanding this unique detoxification mechanism.     

Cartesian causation: body–body interaction, motion, and eternal truths

There is considerable debate among scholars over whether Descartes allowed for genuine body–body interaction. I begin by considering Michael Della Rocca’s recent claim that Descartes accepted such interaction, and that his doctrine of the creation of the eternal truths indicates how this interaction could be acceptable to him. Though I agree that Descartes was inclined to accept real bodily causes of motion, I differ from Della Rocca in emphasizing that his ontology ultimately does not allow for them. This is not the end of the story however, since two of Descartes’s successors offered incompatible ways of developing his conflicted account of motion. I contrast the occasionalist view of Nicolas Malebranche that changes in motion derive directly from divine volitions with the non-occasionalist claim of Pierre-Sylvain Regis that such changes derive from a nature distinct from God. In light of Della Rocca’s interpretation, it is noteworthy that the issue of eternal truths is relevant to both alternative accounts. Indeed, Regis took the doctrine that such truths are created to provide crucial support for his alternative to an occasionalist account of body–body interaction. What does not help Della Rocca, however, is that Regis’s view of motion requires a fundamental revision of Descartes’s ontology.