The Mitragyna speciosa (Kratom) Genome: a resource for data-mining potent pharmaceuticals that impact human health

Mitragyna speciosa (kratom) produces numerous compounds with pharmaceutical properties including the production of bioactive monoterpene indole and oxindole alkaloids. Using a linked-read approach, a 1,122,519,462 bp draft assembly of M. speciosa “Rifat” was generated with an N50 scaffold size of 1,020,971 bp and an N50 contig size of 70,448 bp that encodes 55,746 genes. Chromosome counting revealed that “Rifat” is a tetraploid with a base chromosome number of 11, which was further corroborated by orthology and syntenic analysis of the genome. Analysis of genes and clusters involved in specialized metabolism revealed genes putatively involved in alkaloid biosynthesis. Access to the genome of M. speciosa will facilitate an improved understanding of alkaloid biosynthesis and accelerate the production of bioactive alkaloids in heterologous hosts

Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus‐castus

Vitex agnus‐castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus‐castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus‐castus . With the assistance of matrix‐assisted laser desorption ionisation‐mass spectrometry imaging (MALDI‐MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome‐specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus‐castus . The identified CYP, Vac CYP76BK1, was found to catalyse 16‐hydroxylation of the diol‐diterpene, peregrinol, to labd‐13Z ‐ene‐9,15,16‐triol when expressed in Saccharomyces cerevisiae . Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan‐ and lactone‐containing diterpenoids that are present in this species

Strong "quantum" chaos in the global ballooning mode spectrum of three-dimensional plasmas

The spectrum of ideal magnetohydrodynamic (MHD) pressure-driven (ballooning) modes in strongly nonaxisymmetric toroidal systems is difficult to analyze numerically owing to the singular nature of ideal MHD caused by lack of an inherent scale length. In this paper, ideal MHD is regularized by using a $k$-space cutoff, making the ray tracing for the WKB ballooning formalism a chaotic Hamiltonian billiard problem. The minimum width of the toroidal Fourier spectrum needed for resolving toroidally localized ballooning modes with a global eigenvalue code is estimated from the Weyl formula. This phase-space-volume estimation method is applied to two stellarator cases.Comment: 4 pages typeset, including 2 figures. Paper accepted for publication in Phys. Rev. Letter

SIMAP—structuring the network of protein similarities

Protein sequences are the most important source of evolutionary and functional information for new proteins. In order to facilitate the computationally intensive tasks of sequence analysis, the Similarity Matrix of Proteins (SIMAP) database aims to provide a comprehensive and up-to-date dataset of the pre-calculated sequence similarity matrix and sequence-based features like InterPro domains for all proteins contained in the major public sequence databases. As of September 2007, SIMAP covers ∼17 million proteins and more than 6 million non-redundant sequences and provides a complete annotation based on InterPro 16. Novel features of SIMAP include a new, portlet-based web portal providing multiple, structured views on retrieved proteins and integration of protein clusters and a unique search method for similar domain architectures. Access to SIMAP is freely provided for academic use through the web portal for individuals at http://mips.gsf.de/simap/and through Web Services for programmatic access at http://mips.gsf.de/webservices/services/SimapService2.0?wsdl

Magnetohydrodynamics and Plasma Cosmology

We study the linear magnetohydrodynamic (MHD) equations, both in the Newtonian and the general-relativistic limit, as regards a viscous magnetized fluid of finite conductivity and discuss instability criteria. In addition, we explore the excitation of cosmological perturbations in anisotropic spacetimes, in the presence of an ambient magnetic field. Acoustic, electromagnetic (e/m) and fast-magnetosonic modes, propagating normal to the magnetic field, can be excited, resulting in several implications of cosmological significance.Comment: 9 pages, RevTeX, To appear in the Proceedings of the Peyresq X Meeting, IJTP Conference Serie

Alpha-aminoisobutyric acid uptake in primary cultures of astrocytes

Homotypically pure cultures of rat brain astrocytes were used to examine some aspects of non-neuronal A-system (alanine preferring) amino acid uptake. The Asystem specific probe, alpha-aminoisobutyric acid is transported rapidly, and a steady state distribution ratio of 9–25 is reached after 30 minute incubations. Kinetic estimates derived from uptake progress curves indicated a K m of 1.35 mM and a V max of 133 nmol/min/mg protein. Uptake is reduced in the absence of either Na + or K + . Elevations in extracellular K + , a putative metabolic modulator of neuroglia, did not affect uptake.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45428/1/11064_2004_Article_BF00965086.pd